48

KEY CONCEPTS
Neurons, Synapses,
and Signaling

48.1 Neuron structure and organization

reflect function in information
transfer p. 1068

48.2 Ion pumps and ion channels

establish the resting potential
of a neuron p. 1069

48.3 Action potentials are the signals

conducted by axons p. 1072

48.4 Neurons communicate with other

cells at synapses p. 1077

Study Tip
Figure 48.1 This cone snail (Conus geographus) is slow-moving, but a dangerous
Make a table: The term potential is hunter. Delivering venom with a hollow, harpoon-like tooth, it can paralyze a fish
central to understanding neuronal almost instantaneously. Scuba divers picking up a cone snail have died from a single
signaling, as it provides the driving injection. Underlying the fast-acting, lethal nature of the venom is an ability to block
force for both electrical and chemical information transfer by neurons, specialized cells of the nervous system.
signaling. Fill in a table like this one
as you read to help you distinguish
characteristics of a resting potential, How does a neuron transmit information?
graded potential, and action potential,
A neuron receives information, transmits it along an extension called an axon, and
as well as chemical potentials for sodium transmits the information to other cells via specialized junctions called synapses.
and potassium ion concentrations.

Membrane Occurs in Occurs Variable Input to neuron

potentials cell body? in axon? strength? Sensory information Dendrites
of a neuron or output from other
neurons
Electrical Resting Yes Yes No
Electrical Graded
Electrical Action
Chemical [Na+] Nucleus
Chemical [K+]
Electrical signaling along axon
Electrical impulses travel in one
direction only. Every impulse is
Cell identical, but the frequency of
body signaling varies.
Go to Mastering Biology
Axon
For Students (in eText and Study Area)
• Get Ready for Chapter 48
• BioFlix® Animation: How Neurons Work SYNAPSE
• BioFlix® Animation: How Synapses Work
For Instructors to Assign (in Item Library) Output from neuron
• Scientific Skills Exercise: Interpreting Data Received by muscles,
Values Expressed in Scientific Notation glands,
Synaptic or other
Ready-to-Go Teaching Module terminal neurons
(in Instructor Resources)
Another neuron
• Resting and Action Potentials or other cell
Neurotransmitter
1067
 . Figure 48.3 Summary of information processing. The
CONCEPT 48.1
cone snail’s siphon acts as a sensor, transferring information to

Neuron structure and the neuronal circuits in the snail’s head for processing. If prey is
detected, these circuits issue motor commands—signals that control
organization reflect function muscle activity. In this example, motor commands trigger release
of a harpoon-like tooth from the proboscis, spearing the prey.
in information transfer
Our starting point for exploring the nervous system is the Siphon
neuron, a cell type exemplifying the close fit of form and
Sensory input
function that often arises over the course of evolution.

Integration
Sensor
Neuron Structure and Function
The ability of a neuron to receive and transmit information is
based on the highly specialized cellular organization shown in
Figure 48.1. Most of a neuron’s organelles, including its nucleus, Motor output
are located in the cell body. In a typical neuron, the cell body
Proboscis
is studded with numerous highly branched extensions called
dendrites (from the Greek dendron, tree). Together with the
cell body, the dendrites receive signals from other neurons. Processing center
A typical neuron has a single axon, the extension that
Effector
transmits signals to other cells. Axons are often much longer
than dendrites, and some, such as those that reach from the
spinal cord of a giraffe to the muscle cells in its feet, are over a Mastering Biology
meter long. The specialized structure of axons allows them to Interview with Baldomero Olivera: Developing
drugs from research on cone snail venom
use pulses of electrical current to transmit information, even
over long distances. The cone-shaped base of an axon, called
the axon hillock, is typically where signals that travel down Introduction to Information Processing
the axon are generated. Near its other end, an axon usually Information processing by a nervous system occurs in three
divides into many branches. stages: sensory input, integration, and motor output. As an
Each branched end of an axon transmits information to example, let’s consider the cone snail, focusing on the steps
another cell at a junction called a synapse (Figure 48.2). The involved in identifying and attacking its prey. To generate
part of each axon branch that forms this specialized junction sensory input to the nervous system, the snail surveys its
is a synaptic terminal. At most synapses, chemical messen- environment with sensors in its tubelike siphon, sampling
gers called neurotransmitters pass information from the scents that might reveal a nearby fish (Figure 48.3). During
transmitting neuron to the receiving cell. Cone snail venom the integration stage, networks of neurons in the snail brain
is particularly potent because it interferes not only with elec- process this information to determine if a fish is in fact pres-
trical signaling along axons but also with chemical signaling ent and, if so, where the fish is located. Motor output from
across synapses. the processing center then initiates attack, activating neurons
that trigger release of the harpoon-like tooth toward the prey.
In all but the simplest animals, specialized populations of
. Figure 48.2 Synaptic terminals on the cell body of a neurons handle each stage of information processing.
postsynaptic neuron. (colorized SEM)
• Sensory neurons, like those in the snail’s siphon,
transmit information about external stimuli (such as
light, touch, or smell), and internal conditions (such as
Postsynaptic Synaptic
blood pressure or muscle tension).
neuron terminals
of pre- • Interneurons form the local circuits connecting neurons
synaptic in the brain or ganglia. Interneurons are responsible for the
neurons
integration (analysis and interpretation) of sensory input.
• Motor neurons transmit signals to muscle cells, caus-
ing them to contract. Additional neurons that extend
5 om

out of the processing centers trigger gland activity.

All neurons transmit electrical signals within the cell in an

identical manner. Thus a neuron that detects an odor transmits

1068 UNIT SEVEN Animal Form and Function

information along its length in the same way as a neuron that information processing. Neurons that have highly branched
controls the movement of a body part. The particular connec- dendrites, such as some interneurons, can receive input
tions made by the active neuron are what distinguish the type through tens of thousands of synapses. Similarly, neurons
of information being transmitted. Interpreting nerve impulses that transmit information to many target cells do so through
therefore involves sorting neuronal paths and connections. highly branched axons. When grouped together, the axons of
As shown in Figure 48.4, the shape of a neuron can vary neurons form the bundles we call nerves.
from simple to quite complex, depending on its role in In many animals, the neurons that carry out sorting, pro-
cessing, and integration are organized in a central nervous
system (CNS), which may include a brain or simpler clus-
. Figure 48.4 Structural diversity of neurons. In these drawings ters called ganglia. The neurons that carry information into
of neurons, cell bodies and dendrites are black and axons are red. and out of the CNS constitute the peripheral nervous
Cell system (PNS). Neurons of both the CNS and PNS require
body Dendrites supporting cells called glial cells, or glia (from a Greek word
meaning “glue”) (Figure 48.5).
Axon

CONCEPT CHECK 48.1

Sensory neuron 1. Compare and contrast the structure and function of axons
and dendrites.
2. Describe the basic pathway of information flow through
neurons that causes you to turn your head when someone
calls your name.
3. WHAT IF? How might increased branching of an axon
help coordinate responses to signals communicated by
the nervous system?
Interneuron
For suggested answers, see Appendix A.

CONCEPT 48.2

Ion pumps and ion channels

Motor neuron
establish the resting potential
of a neuron
We turn now to the essential role of ions in neuronal
. Figure 48.5 Glia in the mammalian brain. This fluorescently signaling. In neurons, as in other cells, ions are unequally
labeled laser confocal micrograph shows a region of the rat brain distributed between the interior of cells and the surround-
packed with glia and interneurons. The glia are labeled red, the DNA in ing fluid (see Concept 7.4). As a result, the inside of a cell is
nuclei is labeled blue, and the dendrites of neurons are labeled green.
negatively charged relative to the outside. This charge dif-
ference, or voltage, across the plasma membrane is called the
membrane potential, reflecting the fact that the attrac-
tion of opposite charges across the plasma membrane is a
source of potential energy. For a resting neuron—one that is
not sending a signal—the membrane potential is called the
resting potential and is typically between - 60 and - 80
millivolts (mV).
When a neuron receives a stimulus, the membrane poten-
tial changes. Rapid shifts in membrane potential are what
enable us to see the intricate structure of a spiderweb, hear a
song, or ride a bicycle. These changes, which are known as
action potentials, will be discussed in Concept 48.3. To under-
stand how they convey information, we need to explore the

80 om
ways in which membrane potentials are formed, maintained,
Glia Cell bodies of neurons and altered.

CHAPTER 48 Neurons, Synapses, and Signaling 1069

Formation of the Resting Potential charge. Furthermore, ions can move quite rapidly through
ion channels. When this occurs, the resulting current—a net
Potassium ions (K +) and sodium ions (Na+) play an essential
movement of positive or negative charge—generates a mem-
role in the formation of the resting potential. These ions each
brane potential, or voltage across the membrane.
have a concentration gradient across the plasma membrane
Concentration gradients of ions across a plasma mem-
of a neuron (Table 48.1). In most neurons, the concentration
brane represent a chemical form of potential energy that can
of K + is higher inside the cell, while the concentration of Na+
be harnessed for cellular processes (see Figure 44.17). In neu-
is higher outside. The Na+ and K + concentration gradients are
rons, the ion channels that convert this chemical potential
maintained by the sodium-potassium pump. This pump
energy to electrical potential energy can do so because they
uses the energy of ATP hydrolysis to actively transport Na+ out
have selective permeability, allowing only certain ions to pass.
of the cell and K + into the cell. (There are also concentration
For example, a potassium channel allows K + to diffuse freely
gradients for chloride ions (Cl - ) and other anions, as shown in
across the membrane, but not other ions, such as Na+ or Cl - .
Table 48.1, but we can ignore these for now.)
Diffusion of K + through potassium channels that are
Table 48.1 Ion Concentrations Inside and Outside always open (sometimes called leak channels) is critical for
of Mammalian Neurons establishing the resting potential (Figure 48.7). The K +
Intracellular Extracellular
Concentration Concentration . Figure 48.7 The basis of the membrane potential. The
Ion (mM) (mM)
sodium-potassium pump generates and maintains the concentration
Potassium (K + ) 140 5 gradients of Na+ and K + shown in Table 48.1. The [Na+ ] gradient
results in very little net diffusion of Na+ in a resting neuron because
Sodium (Na+ ) 15 150
very few sodium channels are open. In contrast, the many open
Chloride (Cl - ) 10 120 potassium channels allow a significant net outflow of K + . Because the
membrane is only weakly permeable to chloride and other anions,
Large anions (A - ), such 100 Not applicable this outflow of K + results in a net negative charge inside the cell.
as proteins, inside cell

The sodium-potassium pump transports three Na+ out of

the cell for every two K + that it transports in (Figure 48.6).
Although this pumping generates a net export of positive
charge, the pump acts slowly. The resulting change in the
membrane potential is therefore quite small—only a few mil-
livolts. Why, then, is there a membrane potential of - 60 to
- 80 mV in a resting neuron? The answer lies in ion movement
through ion channels, pores formed by clusters of specialized OUTSIDE OF CELL

proteins that span the membrane. Ion channels allow ions to

diffuse back and forth across the membrane. As ions diffuse
through channels, they carry with them units of electrical

b Figure 48.6 Summary + + + + + + +

OUTSIDE OF CELL of active transport by the
sodium-potassium pump.
You can find a step-by-step – – – – – – –
Na+/K+ 3 Na+ description of the pump’s
pump activity in Figure 7.15.

INSIDE OF CELL

Key

ATP Na+ Sodium-

potassium Potassium Sodium
K+ pump channel channel
2 K+
? The potassium and sodium channels have the same rough overall
INSIDE OF CELL structure, as shown. How must these proteins differ to allow passage of
only a particular ion?

Mastering Biology BioFlix® Animation: Resting Potential

1070 UNIT SEVEN Animal Form and Function

concentration is 140 millimolar (mM) inside the cell, but only The magnitude of the membrane voltage at equilibrium for
5 mM outside. The chemical concentration gradient thus a particular ion is called that ion’s equilibrium potential
favors a net outflow of K + . Furthermore, a resting neuron has (Eion). For a membrane permeable to a single type of ion, Eion
many open potassium channels, but very few open sodium can be calculated using a formula called the Nernst equation.
channels. Because Na+ and other ions can’t readily cross the At human body temperature (37°C) and for an ion with a net
membrane, K + outflow leads to a net negative charge inside charge of 1+, such as K + or Na+ , the Nernst equation is
the cell. This buildup of negative charge within the neuron is
3ion4 outside
the major source of the membrane potential. Eion = 62 mV a log b
3ion4 inside
What stops the buildup of negative charge? The excess
negative charges inside the cell exert an attractive force that Plugging the K + concentrations into the Nernst equation
opposes the flow of additional positively charged potassium reveals that the equilibrium potential for K + (EK) is - 90 mV
ions out of the cell. The separation of charge (voltage) thus (see Figure 48.8a). The minus sign indicates that K + is at equi-
results in an electrical gradient that counterbalances the librium when the inside of the membrane is 90 mV more
chemical concentration gradient of K + . negative than the outside.
Whereas the equilibrium potential for K + is - 90 mV,
the resting potential of a mammalian neuron is somewhat
Modeling the Resting Potential less negative. This difference reflects the small but steady
The net flow of K + out of a neuron proceeds until the chemi- movement of Na+ across the few open sodium channels in
cal and electrical forces are in balance. We can model this a resting neuron. The concentration gradient of Na+ has a
process by considering a pair of chambers separated by an direction opposite to that of K + (see Table 48.1). Na+ there-
artificial membrane. To begin, imagine that the membrane fore diffuses into the cell, making the inside of the cell less
contains many open ion channels, all of which allow only K + negative. If we model a membrane in which the only open
to diffuse across (Figure 48.8a). To produce a K + concentra- channels are selectively permeable to Na+ , we find that a
tion gradient like that of a mammalian neuron, we place a tenfold higher concentration of Na+ in the outer cham-
solution of 140 mM potassium chloride (KCl) in the inner ber results in an equilibrium potential (ENa) of + 62 mV
chamber and 5 mM KCl in the outer chamber. The K + will (Figure 48.8b). In an actual neuron, the resting potential
diffuse down its concentration gradient into the outer cham- ( - 60 to - 80 mV) is much closer to EK than to ENa because
ber. But because the chloride ions (Cl - ) lack a means of cross- there are many open potassium channels but only a small
ing the membrane, there will be an excess of negative charge number of open sodium channels.
in the inner chamber. Because neither K + nor Na+ is at equilibrium in a rest-
When our model neuron reaches equilibrium, the electri- ing neuron, there is a net flow of each ion across the mem-
cal gradient will exactly balance the chemical gradient so that brane. The resting potential remains steady, which means
no further net diffusion of K + occurs across the membrane. that these K + and Na+ currents are equal and opposite. Ion

c Figure 48.8 Modeling a mammalian

Inner –90 mV Outer Inner +62 mV Outer
neuron. In this model of the membrane
chamber chamber chamber chamber
potential of a resting neuron, an artificial
membrane divides each container into two
chambers. Ion channels allow free diffusion 140 mM – + 5 mM 15 mM + – 150 mM
for particular ions, resulting in the net ion KCI NaCI
flow represented by arrows. (a) The presence
KCI NaCI
of open potassium channels makes the
membrane selectively permeable to K +, and – + Cl– + –
the inner chamber contains a 28-fold higher
concentration of K + than the outer chamber; K+ Na+
at equilibrium, the inside of the membrane Cl–
Potassium Sodium
is -90 mV relative to the outside. (b) The
channel – + channel + –
membrane is selectively permeable to Na+, and Artificial
the inner chamber contains a tenfold lower membrane
concentration of Na+ than the outer chamber;
at equilibrium, the inside of the membrane is
+62 mV relative to the outside.
(a) Membrane selectively permeable to K+ (b) Membrane selectively permeable to Na+
Nernst equation for K+ equilibrium Nernst equation for Na+ equilibrium
WHAT IF? How would adding potassium or potential at 37°C: potential at 37°C:
chloride channels to the membrane in (b) affect
the membrane potential?
5 mM 150 mM
EK = 62 mV log ––––––– = – 90 mV ENa = 62 mV log ––––––– = +62 mV
140 mM 15 mM

CHAPTER 48 Neurons, Synapses, and Signaling 1071

concentrations on either side of the membrane also remain . Figure 48.10 Voltage-gated ion channel. A change in the
steady. Why? The resting potential arises from the net move- membrane potential in one direction (solid arrow) opens the
voltage-gated channel. The opposite change (dotted arrow) closes
ment of far fewer ions than would be required to alter the con-
the channel.
centration gradients.
If Na+ is allowed to cross the membrane more readily, the Ions
membrane potential will move toward ENa and away from EK. Change in
As you’ll see, this happens in generation of a nerve impulse. membrane
potential
Mastering Biology Animation: Membrane Potentials (voltage)

CONCEPT CHECK 48.2

1. Under what circumstances could ions flow through an

ion channel from a region of lower ion concentration to a
Ion
region of higher ion concentration? channel
2. WHAT IF? Suppose a cell’s membrane potential shifts from
-70 mV to -50 mV. What changes in the cell’s permeability Gate closed: No ions Gate open: Ions flow
to K + or Na+ could cause such a shift? flow across membrane. through channel.
3. MAKE CONNECTIONS Review Figure 7.11, which illustrates
the diffusion of dye molecules across a membrane. Could dif- VISUAL SKILLS Gated ion channels allow ion flow in either direction.
fusion eliminate the concentration gradient of a dye that has Using visual information in this figure, explain why there is net ion
a net charge? Explain. movement when the channel opens.

For suggested answers, see Appendix A.

you will see, such recordings have been central to the study of
CONCEPT 48.3 information transfer by neurons.
How does a stimulus alter the membrane potential? Certain
Action potentials are the signals ion channels in a neuron, called gated ion channels, open
conducted by axons or close in response to stimuli. When a gated ion channel
opens or closes, it alters the membrane’s permeability to par-
When a neuron responds to a stimulus, the membrane poten-
ticular ions (Figure 48.10). The result is a rapid flow of ions
tial changes. Using intracellular recording, researchers can
across the membrane, altering the membrane potential.
monitor these changes as a function of time (Figure 48.9). As
Particular types of gated channels respond to different
. Figure 48.9 Research Method stimuli. For example, Figure 48.10 illustrates a voltage-
gated ion channel, a channel that opens or closes in
Intracellular Recording response to a shift in the voltage across the plasma mem-
brane of the neuron. Later in this chapter, we will discuss
Application Electrophysiologists use intracellular recording
to measure the membrane potential of neurons and other gated channels that are located in neurons and are regulated
cells. by chemical signals.
Technique A microelectrode is made from a glass capillary
tube filled with an electrically conductive salt solution. Hyperpolarization and Depolarization
One end of the tube tapers to an extremely fine tip
(diameter < 1 µm). While looking through a microscope, Let’s consider now what happens in a neuron when a
the experimenter uses a micropositioner to insert the tip of stimulus causes closed voltage-gated ion channels to open.
the microelectrode into a cell. A voltage recorder (usually If gated potassium channels in a resting neuron open, the
an oscilloscope or a computer-based system) measures the
voltage between the microelectrode tip inside the cell and a membrane’s permeability to K + increases. As a result, net
reference electrode placed in the solution outside the cell. diffusion of K + out of the neuron increases, shifting the
membrane potential toward EK (- 90 mV at 37°C). This
increase in the magnitude of the membrane potential, called
Microelectrode
a hyperpolarization, makes the inside of the membrane
Voltage more negative (Figure 48.11a). In a resting neuron, hyperpo-
recorder
larization results from any stimulus that increases the outflow
of positive ions or the inflow of negative ions.
Although opening potassium channels in a resting neu-
Reference ron causes hyperpolarization, opening some other types of
electrode
ion channels has an opposite effect, making the inside of the
membrane less negative (Figure 48.11b). A reduction in the

1072 UNIT SEVEN Animal Form and Function

. Figure 48.11 Graded potentials and an action potential in a neuron.

Stimulus Stimulus Strong depolarizing stimulus

+50 +50 +50
Action
potential
Membrane potential (mV)

Membrane potential (mV)

Membrane potential (mV)

0 0 0

–50 Threshold –50 Threshold –50 Threshold

Resting Resting Resting

potential potential potential
Hyperpolarizations Depolarizations
–100 –100 –100
0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5 6
Time (msec) Time (msec) Time (msec)

(a) Graded hyperpolarizations produced (b) Graded depolarizations produced by (c) Action potential triggered by a
by two stimuli that increase membrane two stimuli that increase membrane depolarization that reaches the
permeability to K+. The larger stimulus permeability to Na+. The larger stimulus threshold.
produces a larger hyperpolarization. produces a larger depolarization.

DRAW IT Redraw the graph in (c), extending the y-axis. Then label the positions of EK and ENa.

magnitude of the membrane potential is a depolarization. In called threshold, the voltage-gated sodium channels
neurons, depolarization often involves gated sodium channels. open. The resulting flow of Na+ into the neuron results in
If a stimulus causes gated sodium channels to open, the mem- further depolarization. Because the sodium channels are
brane’s permeability to Na+ increases. Na+ diffuses into the cell voltage gated, the increased depolarization causes more
along its concentration gradient, causing a depolarization as sodium channels to open, leading to an even greater flow
the membrane potential shifts toward ENa (+62 mV at 37°C). of current. The result is a process of positive feedback
that triggers a very rapid opening of many voltage-gated
sodium channels and the marked temporary change in
Graded Potentials and Action Potentials membrane potential that defines an action potential
Sometimes, the response to hyperpolarization or depolariza- (Figure 48.11c).
tion is simply a shift in the membrane potential. This shift, The positive-feedback loop of channel opening and
called a graded potential, has a magnitude that varies depolarization triggers an action potential whenever the mem-
with the strength of the stimulus: A larger stimulus causes brane potential reaches threshold, about - 55 mV for many
a greater change in the membrane potential (see Figure mammals. Once initiated, the action potential has a mag-
48.11a and 48.11b). Graded potentials induce a small elec- nitude that is independent of the strength of the triggering
trical current that dissipates as it flows along the membrane. stimulus. Because action potentials either occur fully or do not
Graded potentials thus decay with time and with distance occur at all, they represent an all-or-none response to stimuli.
from their source.
If a depolarization shifts the membrane potential sufficiently,
the result is a massive change in membrane voltage called an
Generation of Action Potentials:
action potential. Unlike graded potentials, action potentials A Closer Look
have a constant magnitude and can regenerate in adjacent The characteristic shape of the action potential graph in
regions of the membrane. Action potentials can therefore spread Figure 48.11c reflects changes in membrane potential result-
along axons, making them well suited for transmitting a signal ing from ion movement through voltage-gated sodium and
over long distances. potassium channels. Depolarization opens both types of
Action potentials arise because some of the ion chan- channels, but they respond independently and sequentially.
nels in neurons are voltage-gated (see Figure 48.10). If a Sodium channels open first, initiating the action potential. As
depolarization increases the membrane potential to a level the action potential proceeds, sodium channels remain open

CHAPTER 48 Neurons, Synapses, and Signaling 1073

but become inactivated: A portion of the channel protein as depicted in Figure 48.12. 1 When the membrane of the
called an inactivation loop blocks ion flow through the open axon is at the resting potential, most voltage-gated sodium
channel. Sodium channels remain inactivated until after the channels are closed. Some potassium channels are open, but
membrane returns to the resting potential and the channels most voltage-gated potassium channels are closed. 2 When
close. Potassium channels open more slowly than sodium a stimulus depolarizes the membrane, some gated sodium
channels, but remain open and functional until the end of channels open, allowing more Na+ to diffuse into the cell.
the action potential. If the stimulus is sufficiently strong, the Na+ inflow persists,
To understand further how voltage-gated channels shape causing further depolarization, which opens more gated
the action potential, consider the process as a series of stages, sodium channels, allowing even more Na+ to diffuse into the

. Figure 48.12 The role of voltage-gated ion channels in the generation of an action potential.
The circled numbers on the graph in the center and the colors of the action potential phases correspond to
the five diagrams showing voltage-gated sodium and potassium channels in a neuron’s plasma membrane.

Key

Na+
– – – – – – – –
K+
+ + + + + + + +
+ + + + + + + +

– – – – – – – –

3 Rising phase of the action potential

Depolarization opens most sodium channels,
while the potassium channels remain 4 Falling phase of the action potential
closed. Na+ influx makes the inside of Most sodium channels
the membrane positive with respect to +50 become inactivated,
the outside. blocking Na+ inflow. Most
Action
potential potassium channels
open, permitting K+
Membrane potential

3 outflow, which makes

0 the inside of the cell
+ + + + + + + + negative again.
(mV)

2 4
– – – – – – – – Threshold
–50
1 1
5
Resting potential
2 Depolarization A stimulus opens some
sodium channels. Na+ inflow through those –100
channels depolarizes the membrane. If the Time
depolarization reaches the threshold, it triggers
an action potential.

OUTSIDE OF CELL Sodium Potassium + + + + + + + +

channel channel

+ + + + + + + + + + + + + + + – – – – – – – –

– – – – – – – – – – – – – – –
INSIDE OF CELL 5 Undershoot The sodium channels close, but
some potassium channels are still open. As these
Inactivation loop
potassium channels close and the sodium
channels become unblocked (though still closed),
1 Resting state The gated Na+ and K+ channels are closed. the membrane returns to its resting state.
Ungated channels (not shown) maintain the resting potential.

DRAW IT Draw a simple diagram showing how positive feedback underlies the rising Mastering Biology BioFlix® Animation:
phase of the action potential. Your diagram should include these three events: (1) a change Action Potential
in membrane potential; (2) ion flow; and (3) opening, closing, or inactivation of a channel.

1074 UNIT SEVEN Animal Form and Function

cell. 3 Once the threshold is crossed, the positive-feedback . Figure 48.13 Conduction of an action potential. This figure
cycle then rapidly brings the membrane potential close to shows events at three successive times as an action potential passes from
left to right. At each point along the axon, voltage-gated ion channels
ENa. This stage of the action potential is called the rising phase.
go through the sequence of changes shown in Figure 48.9. Membrane
4 Two events prevent the membrane potential from actually colors correspond to the action potential phases in that figure.
reaching ENa: Voltage-gated sodium channels inactivate soon
after opening, halting the flow of Na+ into the cell, and most
voltage-gated potassium channels open, causing a rapid out-
flow of K + . Both events quickly bring the membrane potential Axon
back toward EK. This stage is called the falling phase. 5 In the
final phase of an action potential, called the undershoot, the
membrane’s permeability to K + is higher than at rest, so Plasma
the membrane potential is closer to EK than it is at the resting Action membrane
potential
potential. The gated potassium channels eventually close, and – – + + + + + +
the membrane potential returns to the resting potential.
+ + – – – – – –
Why is inactivation of channels required during an Na+ Cytosol
action potential? Because they are voltage gated, the sodium + + – – – – – –
channels open when the membrane potential reaches – – + + + + + +
the threshold of - 55 mV and don’t close until the resting
1 An action potential is generated as Na+ flows inward across
potential is restored. They are therefore open throughout the membrane in one region.
the action potential. However, the resting potential cannot
be restored unless the flow of Na+ into the cell stops. This is
accomplished by inactivation. The sodium channels remain Action
K+ potential
in the “open” state, but sodium ions cease flowing once inac- + + – – + + + +
tivation occurs. The end of Na+ inflow allows K + outflow to
– – + + – – – –
repolarize the membrane. Na+
The sodium channels remain inactivated during the fall- – – + + – – – –
ing phase and the early part of the undershoot. As a result, if + + – – + + + +
a second depolarizing stimulus occurs during this period, it K+
will be unable to trigger an action potential. The “downtime” 2 The depolarization of the action potential spreads to the
when a second action potential cannot be initiated is called neighboring region of the membrane, reinitiating the action
potential there. To the left of this region, the membrane is
the refractory period. Note that the refractory period is repolarizing as K+ flows outward.
due to the inactivation of sodium channels, not to a change
in the ion concentration gradients across the plasma mem-
brane. The flow of charged particles during an action poten- Action
tial involves far too few ions to change the concentration on K+ potential
+ + + + – – + +
either side of the membrane significantly.
– – – – + + – –
Na+
– – – – + + – –
Conduction of Action Potentials
+ + + + – – + +
Having described the events of a single action potential, we’ll K+
explore next how a series of action potentials moves a signal 3 The depolarization-repolarization process is repeated in the
along an axon. At the site where an action potential is initiated next region of the membrane. In this way, local currents of
(usually the axon hillock), Na+ inflow during the rising phase ions across the plasma membrane cause the action potential to
be propagated along the length of the axon.
creates an electrical current that depolarizes the neighboring
DRAW IT For the axon segment shown, consider a point at the left end,
region of the axon membrane (Figure 48.13). The depolariza-
a point in the middle, and a point at the right end. Draw a graph for each
tion is large enough to reach threshold, causing an action point showing the change in membrane potential over time at that point
potential in the neighboring region. This process is repeated as a single nerve impulse moves from left to right across the segment.
many times along the length of the axon. Because an action Mastering Biology BioFlix® Animation: Conduction of an
potential is an all-or-none event, the magnitude and duration Action Potential
of the action potential are the same at each position along the
axon. The net result is the movement of a nerve impulse from An action potential that starts at the axon hillock moves
the cell body to the synaptic terminals, much like the cascade along the axon only toward the synaptic terminals. Why?
of events triggered by knocking over the first domino in a line. Immediately behind the traveling zone of depolarization, the

CHAPTER 48 Neurons, Synapses, and Signaling 1075

sodium channels remain inactivated, making the membrane to danger or opportunity. As a consequence, natural selection
temporarily refractory (not responsive) to further input. often results in anatomical adaptations that increase conduc-
Consequently, the inward current that depolarizes the axon tion speed. One such adaptation is a wider axon. In the same
membrane ahead of the action potential cannot produce way that a wide hose offers less resistance to the flow of water
another action potential behind it. This is why action poten- than does a narrow hose, a wide axon provides less resistance
tials do not travel back toward the cell body. to the current associated with an action potential than does a
After the refractory period is complete, depolarization of narrow axon.
the axon hillock to threshold will trigger a new action poten- In invertebrates, conduction speed varies from several cen-
tial. In many neurons, action potentials last less than 2 mil- timeters per second in very narrow axons to approximately
liseconds (msec), and the firing rate can thus reach hundreds 30 m/sec in the giant axons of some arthropods and molluscs.
of action potentials per second. These giant axons (up to 1 mm in diameter) function in rapid
The frequency of action potentials conveys information: behavioral responses, such as the muscle contraction that
The rate at which action potentials are produced in a par- propels a hunting squid toward its prey.
ticular neuron is proportional to input signal strength. In Vertebrate axons have narrow diameters but can still
hearing, for example, louder sounds result in more frequent conduct action potentials at high speed. How is this
action potentials in neurons connecting the ear to the brain. possible? The evolutionary adaptation that enables fast
Similarly, increased frequency of action potentials in a neu- conduction in vertebrate axons is electrical insulation,
ron that stimulates skeletal muscle tissue will increase the analogous to the plastic insulation that encases many elec-
tension in the contracting muscle. Differences in the number trical wires. Insulation causes the depolarizing current asso-
of action potentials in a given time are in fact the only vari- ciated with an action potential to travel farther along the
able in how information is encoded and transmitted along axon interior, bringing more distant regions to the thresh-
an axon. old sooner.
Gated ion channels and action potentials have a central The electrical insulation that surrounds vertebrate axons
role in nervous system activity. As a consequence, mutations is called a myelin sheath (Figure 48.14). Myelin sheaths
in genes that encode ion channel proteins can cause disor- are produced by glia: oligodendrocytes in the CNS and
ders affecting the nerves or brain—or the muscles or heart, Schwann cells in the PNS. During development, these spe-
depending largely on where in the body the gene for the ion cialized glia wrap axons in many layers of membrane. The
channel protein is expressed. For example, mutations affect- membranes forming these layers are mostly lipid, which is a
ing voltage-gated sodium channels in skeletal muscle cells poor conductor of electrical current and thus a good insulator.
can cause myotonia, a periodic spasming of those muscles. In myelinated axons, voltage-gated sodium channels
Mutations affecting sodium channels in the brain can cause are restricted to gaps in the myelin sheath called nodes of
epilepsy, in which groups of nerve cells fire simultaneously Ranvier (see Figure 48.14). Furthermore, the extracellular
and excessively, producing seizures. fluid is in contact with the axon membrane only at the nodes.
As a result, action potentials are not generated in the regions
Evolutionary Adaptations of Axon Structure between the nodes. Rather, the inward current produced dur-
EVOLUTION The rate at which the axons within nerves con- ing the rising phase of the action potential at a node travels
duct action potentials governs how rapidly an animal can react within the axon all the way to the next node. There, the current

. Figure 48.14 Schwann cells and the myelin sheath. In the PNS, glia called Schwann cells wrap
themselves around axons, forming layers of myelin. Gaps between adjacent Schwann cells are called nodes
of Ranvier. The TEM shows a cross section through a myelinated axon.

Node of Ranvier

Layers of myelin
Axon

Myelin sheath
(Schwann cell) Schwann
cell
Nodes of Nucleus of
Axon
Ranvier Schwann cell

0.1 om

1076 UNIT SEVEN Animal Form and Function

. Figure 48.15 Propagation of action potentials in myelinated axons. In a myelinated
axon, the depolarizing current during an action potential at one node of Ranvier spreads along
the interior of the axon to the next node (blue arrows), where voltage-gated sodium channels
enable reinitiation. Thus, the action potential appears to jump from node to node as it travels
along the axon (red arrows).

Schwann cell (myelin sheath)

Depolarized region
(node of Ranvier)

Cell body
– – – Myelin
+ +
+ + +
– –
+ + Axon
+
– – – –
–
+ +

Mastering Biology Animation: Propagation of an Action Potential in Unmyelinated

and Myelinated Axons

depolarizes the membrane and regenerates the action potential CONCEPT 48.4
(Figure 48.15).
Action potentials propagate more rapidly in myelinated Neurons communicate with
axons because the time-consuming process of opening and
closing of ion channels occurs at only a limited number of
other cells at synapses
positions along the axon. This mechanism for propagating Transmission of information from neurons to other cells
action potentials is called saltatory conduction (from the occurs at synapses. Synapses are either electrical or chemical.
Latin saltare, to leap) because the action potential appears to Electrical synapses contain gap junctions (see Figure 6.30)
jump from node to node along the axon. that allow electrical current to flow directly from one neuron to
The major selective advantage of myelination is its space another. Such synapses often play a role in synchronizing the
efficiency. A myelinated axon 20 µm in diameter has a con- activity of neurons that direct rapid, unvarying behaviors. For
duction speed faster than that of a squid giant axon with a example, electrical synapses associated with the giant axons of
diameter 40 times greater. Consequently, more than 2,000 of squids and lobsters facilitate swift escapes from danger. Electrical
those myelinated axons can be packed into the space occu- synapses are also found in the vertebrate heart and brain.
pied by just one giant axon. The majority of synapses are chemical synapses, which rely
For any axon, myelinated or not, the conduction of an on the release of a chemical neurotransmitter by the presyn-
action potential to the end of the axon sets the stage for the aptic neuron to transfer information to the target cell. While
next step in neuronal signaling—the transfer of information at rest, the presynaptic neuron synthesizes the neurotrans-
to another cell. This information handoff occurs at synapses, mitter at each synaptic terminal, packaging it in multiple
our next topic. membrane-enclosed compartments called synaptic vesicles.
When an action potential arrives at a chemical synapse, it
depolarizes the plasma membrane at the synaptic terminal,
CONCEPT CHECK 48.3
opening voltage-gated channels that allow Ca2+ to diffuse in.
The Ca2+ concentration in the terminal rises, causing synaptic
1. How do action potentials and graded potentials differ?
vesicles to fuse with the terminal membrane and release the
2. In multiple sclerosis (from the Greek skleros, hard), a per-
son’s myelin sheaths harden and deteriorate. How would
neurotransmitter.
this affect nervous system function? Neurotransmitter released from the synaptic terminus
3. How do both negative and positive feedback contribute diffuses across the synaptic cleft, the gap that separates the
to the changes in membrane potential during an action presynaptic neuron from the postsynaptic cell. Diffusion
potential?
time is very short because the gap is less than 50 nm across.
4. WHAT IF? Suppose a mutation caused gated sodium chan-
Upon reaching the postsynaptic membrane, the neurotrans-
nels to remain inactivated longer after an action potential.
How would this affect the frequency at which action poten- mitter binds to and activates a specific receptor in the mem-
tials could be generated? Explain. brane. This series of events at the synapse is summarized
For suggested answers, see Appendix A. in Figure 48.16.

CHAPTER 48 Neurons, Synapses, and Signaling 1077

. Figure 48.16 A chemical synapse. This figure illustrates the sequence of events that transmits a signal across
a chemical synapse. In response to binding of neurotransmitter, ligand-gated ion channels in the postsynaptic
membrane open (as shown here) or, less commonly, close. Synaptic transmission ends when the neurotransmitter
diffuses out of the synaptic cleft, is taken up by the synaptic terminal or by another cell, or is degraded by an enzyme.

WHAT IF? If all the Ca2+ in the fluid surrounding

Presynaptic cell Postsynaptic cell a neuron were removed, how would this affect the
transmission of information within and between neurons?

Mastering Biology BioFlix® Animation:

How Synapses Work
HHMI Videos: Baldomero Olivera
Axon on the Deadly Conus geographicus •
Blockage of Motor Neuron
Synapses by Cone Snail Toxins
Synaptic vesicle
containing Synaptic
neurotransmitter cleft
Postsynaptic
membrane

Presynaptic
membrane

K+

Ca2+

Voltage-gated Ligand-gated
Ca2+ channel ion channels Na+

1 An action 2 The depolarization 3 2+ concentration 4

potential arrives, opens voltage-gated ion channels in the postsynaptic membrane.
depolarizing channels, triggering an the presynaptic membrane,
the presynaptic 2+. + and K+
membrane.

Information transfer at chemical synapses can be modi- ions to diffuse across the postsynaptic membrane. The
fied by altering either the amount of neurotransmitter that is result is a postsynaptic potential, a graded potential in the
released or the responsiveness of the postsynaptic cell. Such postsynaptic cell.
modifications underlie an animal’s ability to alter its behavior At some chemical synapses, the ligand-gated ion chan-
in response to change and also form the basis for learning and nels are permeable to both K + and Na+ (see Figure 48.16).
memory, as you will read in Concept 49.4. When these channels open, the membrane potential depo-
larizes toward a value roughly midway between EK and
ENa. Because such a depolarization brings the membrane
Generation of Postsynaptic Potentials potential toward threshold, it is called an excitatory
At many chemical synapses, the receptor protein that binds postsynaptic potential (EPSP).
and responds to neurotransmitters is a ligand-gated At other chemical synapses, the ligand-gated ion
ion channel, often called an ionotropic receptor. These channels are selectively permeable for only K + or Cl - . When
receptors are clustered in the membrane of the postsynap- such channels open, the postsynaptic membrane hyperpo-
tic cell, directly opposite the synaptic terminal. Binding of larizes. A hyperpolarization produced in this manner is an
the neurotransmitter (the receptor’s ligand) to a particular inhibitory postsynaptic potential (IPSP) because it
part of the receptor opens the channel and allows specific moves the membrane potential farther from threshold.

1078 UNIT SEVEN Animal Form and Function

Summation of Postsynaptic Potentials neuron. If such synapses are active at the same time, the
resulting EPSPs can add together through spatial summation
The interplay between multiple excitatory and inhibitory
(Figure 48.17c).
inputs is the essence of integration in the nervous system. The
Summation applies as well to IPSPs: Two or more IPSPs
cell body and dendrites of a given postsynaptic neuron may
occurring nearly simultaneously at synapses in the same
receive inputs from chemical synapses formed with hundreds
region or in rapid succession at the same synapse have a
or even thousands of synaptic terminals (see Figure 48.2).
larger hyperpolarizing effect than a single IPSP. Through
How do so many synapses contribute to information transfer?
summation, an IPSP can also counter the effect of an EPSP
The input from an individual synapse is typically insuf-
(Figure 48.17d).
ficient to trigger a response in a postsynaptic neuron. To see
The axon hillock is the neuron’s integrating center, the
why, consider an EPSP arising at a single synapse. As a graded
region where the membrane potential at any instant repre-
potential, the EPSP becomes smaller as it spreads from the
sents the summed effect of all EPSPs and IPSPs. Whenever the
synapse. Therefore, by the time a particular EPSP reaches the
membrane potential at the axon hillock reaches threshold, an
axon hillock, it is usually too small to trigger an action poten-
action potential is generated and travels along the axon to its
tial (Figure 48.17a).
synaptic terminals. After the refractory period, the neuron may
On some occasions, individual postsynaptic potentials
produce another action potential, provided the membrane
combine to produce a larger postsynaptic potential, a pro-
potential at the axon hillock once again reaches threshold.
cess called summation. For instance, two EPSPs may occur
at a single synapse in rapid succession. If the second EPSP
arises before the postsynaptic membrane potential returns
Termination of Neurotransmitter
to its resting value, the EPSPs add together through temporal Signaling
summation. If the summed postsynaptic potentials depo- After a response is triggered, the chemical synapse returns
larize the membrane at the axon hillock to threshold, the to its resting state. How does this happen? The key step is
result is an action potential (Figure 48.17b). Summation can clearing the neurotransmitter molecules from the synaptic
also involve multiple synapses on the same postsynaptic cleft. Some neurotransmitters are inactivated by enzymatic

. Figure 48.17 Summation of postsynaptic potentials. These graphs trace changes in the membrane Mastering Biology
potential at a postsynaptic neuron’s axon hillock. The red arrows indicate times when postsynaptic Animation: Action Potentials
potentials occur at two excitatory synapses (E1 and E2, green in the diagrams above the graphs) and at one
inhibitory synapse (I, purple). Like most EPSPs, those produced at E1 or E2 do not reach the threshold at the
axon hillock without summation.

Terminal branch
E1 of presynaptic E1 E1 E1
neuron
E2 E2 E2 E2

Postsynaptic Axon
neuron hillock
I I I I
Membrane potential (mV)

0
Threshold of axon of Action Action
postsynaptic neuron potential potential
Resting
potential

–70
E1 E1 E1 E1 E1 + E2 E1 I E1 + I

(a) Subthreshold, (b) Temporal summation (c) Spatial summation (d) Spatial summation
no summation of EPSP and IPSP

VISUAL SKILLS Using these drawings, propose an argument for all summation being in some sense temporal.

CHAPTER 48 Neurons, Synapses, and Signaling 1079

. Figure 48.18 Two mechanisms of terminating Consider, for example, the metabotropic receptor for the
neurotransmission. neurotransmitter norepinephrine. Binding of norepineph-
PRESYNAPTIC NEURON
rine to its G protein-coupled receptor activates a G pro-
tein, which in turn activates adenylyl cyclase, the enzyme
Neurotransmitter that converts ATP to cAMP (see Figure 11.11). Cyclic AMP
activates protein kinase A, which phosphorylates specific
ion channel proteins in the postsynaptic membrane, caus-
Fragments ing them to open or close. Because of the amplifying effect
Neurotransmitter of inactivated of the signal transduction pathway, the binding of one
receptor neurotransmitter
norepinephrine molecule can trigger the opening or clos-
ing of many channels.
POSTSYNAPTIC NEURON Inactivating enzyme Many neurotransmitters have both ionotropic and metabo-
tropic receptors. Compared with the postsynaptic potentials
(a) Enzymatic breakdown of neurotransmitter in the synaptic cleft
produced by ligand-gated channels, the effects of G protein
pathways typically have a slower onset but last longer.

Neurotransmitters
Neurotransmitter
Signaling at a synapse brings about a response that
Neurotransmitter depends on both the neurotransmitter released from the
Neurotransmitter transport channel presynaptic membrane and the receptor produced at the
receptor
postsynaptic membrane. A single neurotransmitter may
bind specifically to more than a dozen different receptors.
Indeed, a particular neurotransmitter can excite postsyn-
(b) Reuptake of neurotransmitter by presynaptic neuron aptic cells expressing one receptor and inhibit postsynaptic
cells expressing a different receptor. As an example, let’s
examine acetylcholine, a common neurotransmitter in
hydrolysis (Figure 48.18a). Other neurotransmitters are
both invertebrates and vertebrates.
recaptured into the presynaptic neuron (Figure 48.18b). After
this reuptake occurs, neurotransmitters are repackaged in
synaptic vesicles or transferred to glia for metabolism or recy- Acetylcholine
cling to neurons. Acetylcholine is vital for nervous system functions that
Clearing neurotransmitter from the synaptic cleft is an include muscle stimulation, memory formation, and learn-
essential step in the transmission of information through ing. In vertebrates, there are two major classes of acetylcho-
the nervous system. Indeed, blocking this process can have line receptor. One is a ligand-gated ion channel. We know
severe consequences. For example, the nerve gas sarin triggers the most about its function at the vertebrate neuromuscular
paralysis and death because it inhibits the enzyme that breaks junction, the site where a motor neuron forms a synapse with
down the neurotransmitter controlling skeletal muscles. a skeletal muscle cell. When acetylcholine released by motor
neurons binds this receptor, the ion channel opens, produc-
ing an EPSP. This excitatory activity is soon terminated by
Modulated Signaling at Synapses acetylcholinesterase, an enzyme in the synaptic cleft that
So far, we have focused on synapses where a neurotransmitter hydrolyzes the neurotransmitter.
binds directly to an ion channel, causing the channel to open. A G protein-coupled receptor for acetylcholine is found at
However, there are also chemical synapses in which the receptor locations that include the vertebrate CNS and heart. In heart
for the neurotransmitter is not part of an ion channel. At these muscle, acetylcholine released by neurons activates a signal
synapses, the neurotransmitter binds to a G protein-coupled transduction pathway. The G proteins in the pathway inhibit
receptor, activating a signal transduction pathway in the post- adenylyl cyclase and open potassium channels in the muscle
synaptic cell involving a second messenger (see Concept 11.3). cell membrane. Both effects reduce the rate at which the
Because the resulting opening or closing of ion channels heart pumps. Thus, the effect of acetylcholine in heart muscle
depends on one or more metabolic steps, these G protein- is inhibitory rather than excitatory.
coupled receptors are also called metabotropic receptors. Several chemicals with profound effects on the ner-
G protein-coupled receptors modulate the responsive- vous system mimic or alter the function of acetylcholine.
ness and activity of postsynaptic neurons in diverse ways. Nicotine, a chemical found in tobacco and tobacco smoke,

1080 UNIT SEVEN Animal Form and Function

acts as a stimulant by binding to an ionotropic acetylcho- Amino Acids
line receptor in the CNS. As discussed earlier, the nerve gas Glutamate is one of several amino acids that can act as a
sarin blocks enzymatic cleavage of acetylcholine. A third neurotransmitter. In invertebrates, glutamate, rather than
example is botulinum toxin, which inhibits presynaptic acetylcholine, is the neurotransmitter at the neuromuscu-
release of acetylcholine. The result is a form of food poison- lar junction. In vertebrates, glutamate is the most common
ing called botulism. Because muscles required for breath- neurotransmitter in the CNS. Synapses at which glutamate is
ing fail to contract when acetylcholine release is blocked, the neurotransmitter have a key role in the formation of long-
untreated botulism is typically fatal. Today, injections of term memory, as you will see in Concept 49.4.
the botulinum toxin, known by the trade name Botox, are Two amino acids act as inhibitory neurotransmitters in the
used cosmetically to minimize wrinkles around the eyes or CNS. Glycine acts at inhibitory synapses in parts of the CNS
mouth by inhibiting synaptic transmission to particular that lie outside of the brain. Within the brain, the amino acid
facial muscles. gamma-aminobutyric acid (GABA) is the neurotransmitter at
Although acetylcholine has many roles, it is just one of most inhibitory synapses. Binding of GABA to receptors in
more than 100 known neurotransmitters. As shown by the postsynaptic cells increases membrane permeability to Cl - ,
examples in Table 48.2, the rest fall into four classes: amino resulting in an IPSP. The widely prescribed drug diazepam
acids, biogenic amines, neuropeptides, and gases. (Valium) reduces anxiety through binding to a site on a GABA
receptor, increasing the response to GABA.

Biogenic Amines
Table 48.2 Major Neurotransmitters The neurotransmitters grouped as biogenic amines are synthe-
Neurotransmitter Structure sized from amino acids and include norepinephrine, which is
Acetylcholine CH3
made from tyrosine. Norepinephrine is an excitatory neu-
O
rotransmitter in the autonomic nervous system, a branch of
H3C C O CH2 CH2 N+ CH3
the PNS. Outside the nervous system, norepinephrine has dis-
CH3 tinct but related functions as a hormone, as does the chemi-
cally similar biogenic amine epinephrine (see Concept 45.3).
Amino Acids H2N CH CH2 CH2 COOH
The biogenic amines dopamine (made from tyrosine) and
Glutamate COOH
serotonin (made from tryptophan) are released at many sites
GABA (gamma- H2N CH2 COOH in the brain and affect sleep, mood, attention, and learning.
aminobutyric acid)
Some psychoactive drugs, including LSD and mescaline,
Glycine H2N CH2 CH2 CH2 COOH
apparently produce their hallucinatory effects by binding to
brain receptors for these neurotransmitters.
Biogenic Amines HO
Biogenic amines have a central role in a number of ner-
Norepinephrine
HO CH CH2 NH2 vous system disorders and treatments (see Concept 49.5). The
degenerative illness Parkinson’s disease is associated with a
OH
lack of dopamine in the brain. In addition, depression is often
Dopamine HO treated with drugs that increase the brain concentrations of
biogenic amines. Prozac, for instance, enhances the effect of
HO CH2 CH2 NH2
serotonin by inhibiting its reuptake after it is released by pre-
synaptic neurons.
Serotonin HO
C CH2 CH2 NH2
CH
N Neuropeptides
H
Several neuropeptides, relatively short chains of amino acids,
Neuropeptides (a very diverse group, only two of which are shown) serve as neurotransmitters that operate via G protein-coupled
Substance P receptors. Such peptides are typically produced by cleavage of
Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met
much larger protein precursors. The neuropeptide substance P is
Met-enkephalin (an endorphin) a key excitatory neurotransmitter that mediates our perception
Tyr Gly Gly Phe Met of pain. Other neuropeptides, called endorphins, function as
natural analgesics, decreasing pain perception.
Gases
Endorphins are produced in the brain during times of
Nitric oxide N O
physical or emotional stress, such as childbirth. In addition

CHAPTER 48 Neurons, Synapses, and Signaling 1081

Scientific Skills Exercise

Interpreting Data Values Expressed Data from the Experiment

in Scientific Notation Drug Opiate

Lowest Concentration That
Blocked Naloxone Binding

Does the Brain Have Specific Protein Receptors for Morphine Yes 6 * 10-9 M
Opiates? Researchers were looking for opiate receptors in Methadone Yes 2 * 10-8 M
the mammalian brain. Knowing that the drug naloxone blocks
the analgesic effect of opiates, they hypothesized that nalox- Levorphanol Yes 2 * 10-9 M
one acts by binding tightly to brain opiate receptors without Phenobarbital No No effect at 10-4 M
activating them. In this exercise, you will interpret the results
Atropine No No effect at 10-4 M
of an experiment to test this hypothesis.
Serotonin No No effect at 10-4 M
How the Experiment Was Done The researchers incubated ra-
dioactive naloxone with a protein mixture prepared from rodent Data from C. B. Pert and S. H. Snyder, Opiate receptor: demonstration in nervous
tissue, Science 179:1011–1014 (1973).
brains. If the mixture contained opiate receptors or other pro-
teins that could bind naloxone, the radioactivity would stably as-
sociate with the mixture. To determine whether the binding was INTERPRET THE DATA
due to specific opiate receptors, they tested other drugs, opiate
1. The data above are expressed in scientific notation: a numerical
and non-opiate, for their ability to block naloxone binding.
factor times a power of 10. Remember that a negative power
of 10 means a number less than 1. For example, 10-1 M (molar)
Radioactive can also be written as 0.1 M. Write the concentrations in the
naloxone table for morphine and atropine in this alternative format.
2. Compare the concentrations listed in the table for methadone
1 Radioactive
naloxone and a and phenobarbital. Which concentration is higher? By how much?
test drug are Drug 3. Would phenobarbital, atropine, or serotonin have blocked
added to a protein naloxone binding at a concentration of 10-5 M? Explain.
mixture. 4. (a) Which drugs blocked naloxone binding in this experiment?
(b) What do these results indicate about the brain receptors for
naloxone?
5. When the researchers instead used tissue from intestinal muscles
rather than brains, they found no naloxone binding. What does
2 Proteins are trapped on that suggest about opiate receptors in mammalian muscle?
a filter. Bound naloxone
is detected by measuring Instructors: A version of this Scientific Skills Exercise can be
radioactivity. assigned in Mastering Biology.

to relieving pain, they reduce urine output, decrease respira- muscle in the blood vessel walls of the spongy erectile tissue
tion, and produce euphoria as well as other emotional effects. allows the tissue to fill with blood, producing an erection.
Because opiates (drugs such as morphine and heroin) bind The erectile dysfunction drug Viagra works by inhibiting an
to the same receptor proteins as endorphins, opiates mimic enzyme that terminates the action of NO.
endorphins and produce many of the same physiological Unlike most neurotransmitters, NO is not stored
effects (see Figure 2.16). In the Scientific Skills Exercise, you in cytoplasmic vesicles but is instead synthesized on
can interpret data from an experiment designed to search for demand. NO diffuses into neighboring target cells, produces
opiate receptors in the brain. a change, and is broken down—all within a few seconds.
In many of its targets, including smooth muscle cells, NO
works like many hormones, stimulating an enzyme to
Gases synthesize a second messenger that directly affects cellular
Some vertebrate neurons release dissolved gases as neu- metabolism.
rotransmitters. In human males, for example, certain neurons Although the gas carbon monoxide (CO) is a deadly
release nitric oxide (NO) into the erectile tissue of the penis poison if inhaled, vertebrates produce small amounts of
during sexual arousal. The resulting relaxation of smooth CO as a neurotransmitter. For example, CO synthesized

1082 UNIT SEVEN Animal Form and Function

in the brain regulates the release of hormones from the CONCEPT CHECK 48.4
hypothalamus.
1. How is it possible for a particular neurotransmitter to pro-
In the next chapter, we’ll consider how the cellular and duce opposite effects in different tissues?
biochemical mechanisms we have discussed contribute to 2. Some pesticides inhibit acetylcholinesterase, the enzyme
nervous system function on the system level. that breaks down acetylcholine. Explain how these toxins
would affect EPSPs produced by acetylcholine.
Mastering Biology The Visual Brain: Neural Conduction and 3. MAKE CONNECTIONS Name one or more membrane activi-
Synaptic Transmission ties that occur both in fertilization of an egg and in neuro-
transmission across a synapse (see Figure 47.3).
For suggested answers, see Appendix A.

48 Chapter Review Go to Mastering Biology for Assignments, the eText,

the Study Area, and Dynamic Study Modules.

SUMMARY OF KEY CONCEPTS CONCEPT 48.3

Action potentials are the signals conducted by axons
To review key terms, go to the Vocabulary Self-Quiz in the (pp. 1072–1077)
Mastering Biology eText or Study Area, or go to goo.gl/zkjz9t.
• Neurons have gated ion channels that open or close in re-
sponse to stimuli, leading to changes in the membrane potential.
CONCEPT 48.1 An increase in the magnitude of the membrane potential is a
Neuron structure and organization reflect function hyperpolarization; a decrease is a depolarization. Changes
in information transfer (pp. 1068–1069) in membrane potential that vary continuously with the strength
of a stimulus are known as graded potentials.
• Most neurons have branched dendrites that receive signals • An action potential is a brief, all-or-none depolarization of
from other neurons and an axon that transmits signals to other a neuron’s plasma membrane. When a graded depolarization
cells at synapses. Neurons rely on glia for functions that in- brings the membrane potential to threshold, many voltage-
clude nourishment, insulation, and regulation. gated ion channels open, triggering an inflow of Na+ that rap-
idly brings the membrane potential to a positive value. A negative
Dendrites Axon membrane potential is restored by the inactivation of sodium
hillock channels and by the opening of many voltage-gated potassium
Cell body Axon
channels, which increases K + outflow. A refractory period fol-
lows, corresponding to the interval when the sodium channels
Postsynaptic are inactivated.
cell
Action potential
+50
Presynaptic Signal Synapse
cell direction
Membrane potential (mV)

Falling
phase
• A central nervous system (CNS) and a peripheral nervous 0 Rising
system (PNS) together process information in three stages:
phase
sensory input, integration, and motor output to effector cells.

? How would severing an axon affect the flow of information in Threshold (–55)
a neuron? –50
Resting
CONCEPT 48.2 potential
–70 Depolarization Undershoot
Ion pumps and ion channels establish the resting
potential of a neuron (pp. 1069–1072) –100
0 1 2 3 4 5 6
• Ion concentration gradients generate a voltage difference, or Time (msec)
membrane potential, across the plasma membrane of cells.
The concentration of Na+ is higher outside than inside; the re-
verse is true for K + . In resting neurons, the plasma membrane • A nerve impulse travels from the axon hillock to the synaptic
has many open potassium channels but few open sodium chan- terminals by propagating a series of action potentials along the
nels. Diffusion of ions, principally K + , through channels gener- axon. The speed of conduction increases with the diameter of the
ates a resting potential, with the inside more negative than axon and, in many vertebrate axons, with myelination. Action
the outside. potentials in myelinated axons appear to jump from one node of
Ranvier to the next, a process called saltatory conduction.
? Suppose you placed an isolated neuron in a solution similar
to extracellular fluid and later transferred the neuron to a INTERPRET THE DATA Assuming a refractory period equal in
solution lacking any Na + . What change would you expect in the length to the action potential (see graph above), what is the maximum
resting potential? frequency per unit time at which a neuron could fire action potentials?

CHAPTER 48 Neurons, Synapses, and Signaling 1083

 CONCEPT 48.4 6. Suppose a particular neurotransmitter causes an IPSP in
postsynaptic cell X and an EPSP in postsynaptic cell Y. A likely
Neurons communicate with other cells at synapses explanation is that
(pp. 1077–1083) (A) the threshold value in the postsynaptic membrane for cell
X is different from that for cell Y.
• In an electrical synapse, electrical current flows directly from
(B) the axon of cell X is myelinated, but that of cell Y is not.
one cell to another. In a chemical synapse, depolarization causes
(C) only cell Y produces an enzyme that terminates the activity
synaptic vesicles to fuse with the terminal membrane and release
neurotransmitter into the synaptic cleft. of the neurotransmitter.
• At many synapses, the neurotransmitter binds to ligand-gated (D) cells X and Y express different receptor molecules for this
ion channels in the postsynaptic membrane, producing an particular neurotransmitter.
excitatory or inhibitory postsynaptic potential (EPSP or
IPSP). The neurotransmitter then diffuses out of the cleft, is taken Levels 5-6: Evaluating/Creating
up by surrounding cells, or is degraded by enzymes. A single neu-
7. WHAT IF? Ouabain, a plant substance used in some cultures
ron has many synapses on its dendrites and cell body. Temporal
to poison hunting arrows, disables the sodium-potassium
and spatial summation of EPSPs and IPSPs at the axon hillock
pump. What change in the resting potential would you expect
determine whether a neuron generates an action potential.
to see if you treated a neuron with ouabain? Explain.
• Different receptors for the same neurotransmitter produce
different effects. Some neurotransmitter receptors activate sig- 8. WHAT IF? If a drug mimicked the activity of GABA in the CNS,
nal transduction pathways, which can produce long-lasting what general effect on behavior might you expect? Explain.
changes in postsynaptic cells. Major neurotransmitters include
9. DRAW IT Suppose a researcher inserts electrodes at two
acetylcholine; the amino acids GABA, glutamate, and glycine;
positions along the middle of an axon dissected out of a squid.
biogenic amines; neuropeptides; and gases such as NO.
By applying a depolarizing stimulus, the researcher brings the
? Why are many drugs that are used to treat nervous system diseases plasma membrane at both positions to threshold. Using the
or to affect brain function targeted to specific receptors rather than drawing below as a model, create one or more drawings that
particular neurotransmitters? illustrate where each action potential would terminate.
Electrode
TEST YOUR UNDERSTANDING
For more multiple-choice questions, go to the Practice Test in the
Mastering Biology eText or Study Area, or go to goo.gl/GruWRg. Squid axon
Levels 1-2: Remembering/Understanding 10. EVOLUTION CONNECTION An action potential is an all-or-
none event. This on/off signaling is an evolutionary adaptation
1. What happens when a resting neuron’s membrane depolarizes?
of animals that must sense and act in a complex environment.
(A) There is a net diffusion of Na+ out of the cell.
Imagine a nervous system in which the action potentials
(B) The equilibrium potential for K + (EK) becomes more positive.
are graded, with the amplitude depending on the size of the
(C) The neuron’s membrane voltage becomes more positive. stimulus. Describe what evolutionary advantage on/off signaling
(D) The cell’s inside becomes more negative than the outside. might have over this continuously variable kind of signaling.
2. A common feature of action potentials is that they
11. SCIENTIFIC INQUIRY From what you know about action
(A) cause the membrane to hyperpolarize and then depolarize. potentials and synapses, propose two hypotheses for how
(B) can undergo temporal and spatial summation. various anesthetics might block pain.
(C) are triggered by a depolarization that reaches threshold.
(D) move at the same speed along all axons. 12. WRITE ABOUT A THEME: ORGANIZATION In a short essay
(100–150 words), describe how the structure and electrical
3. Where are neurotransmitter receptors located? properties of vertebrate neurons reflect similarities and
(A) the nuclear membrane differences with other animal cells.
(B) the nodes of Ranvier
13. SYNTHESIZE YOUR KNOWLEDGE
(C) the postsynaptic membrane
(D) synaptic vesicle membranes

Levels 3-4: Applying/Analyzing

4. Why are action potentials usually conducted in one direction?
(A) Ions can flow along the axon in only one direction.
(B) The brief refractory period prevents reopening of voltage-
gated Na+ channels.
(C) The axon hillock has a higher membrane potential than the
terminals of the axon.
(D) Voltage-gated channels for both Na+ and K + open in only
one direction.
5. Which of the following is the most direct result of depolarizing
the presynaptic membrane of an axon terminal?
(A) Voltage-gated calcium channels in the membrane open. This diamond-back rattlesnake (Crotalus atrox) alerts enemies
(B) Synaptic vesicles fuse with the membrane. to its presence with a rattle—a set of modified scales at the tip
(C) Ligand-gated channels open, allowing neurotransmitters to of its tail. Describe the roles of gated ion channels in initiating
enter the synaptic cleft. and moving a signal along the nerve from the snake’s head to
(D) An EPSP or IPSP is generated in the postsynaptic cell. its tail and then to the muscle that shakes the rattle.
For selected answers, see Appendix A.
1084 UNIT SEVEN Animal Form and Function