EXCITABLE TISSUES

By

ISA AHMED-SHERIF PhD

DEPARTMENT OF HUMAN PHYSIOLOGY,

FACULTY OF BASIC MEDICAL SCIENCES,

COLLEGE OF MEDICAL SCIENCES

AHMADU BELLO UNIVERSITY, ZARIA

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 EXCITABLE TISSUES

INTRODUCTION
The human central nervous system (CNS) contains about 100 billion neurons. It also contains
10–50 times this number of glial cells. The neurons, the basic building blocks of the nervous
system. The integration and transmission of nerve impulses have become the specialized
functions of neurons. This describes the cellular components of the CNS and the excitability of
neurons, which involves the genesis of electrical signals that enable neurons to integrate and
transmit impulses (action potentials, receptor potentials, and synaptic potentials).

CLASSIFICATION OF NERVE CELLS (NEURONES)

Neurons may be classified according to
1. The number of poles (structural classification)
2. Their function.
3. The length of the axon
1. Classification based on the number of poles
The structural classification of neurons is based on the number of processes or poles that extend
from the cell body of the neuron. They include unipolar,bipolar and multipolar neurons.
I. Unipolar/Pseudounipolar
neurons have a single short process that branches like a T to form a pair of longer processes.
They are called pseudounipolar (pseudo = false) because, though they originate with two
processes, during early embryonic development their two processes converge and partially fuse.
Sensory neurons are pseudounipolar—one of the branched processes receives sensory stimuli
and produces nerve impulses; the other delivers these impulses to synapses within the brain or
spinal cord. Anatomically, the part of the process that conducts impulses toward the cell body
can be considered a dendrite, and the part that conducts impulses away from the cell body can be
considered an axon.
II. Bipolar neurons
These have two processes/poles, among the poles, axon arises from one pole and dendrites from
the other; this type of neurone is found in the retina of the eye.

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III. Multipolar neurons
These are the most common type of neurone, it is characterized by several dendrites and one
axon extending from the cell body; motor neurons are good examples of this type of neurone.

Figure 1: Different types of neurons (From above downwards: unipolar, bipolar and multipolar
neurone)
2. Classification based on function
The functional classification is based on the direction in which they conduct impulses sensory,
or afferent, neurons conduct impulses from sensory receptors into the CNS. motor, or efferent,
neurons conduct impulses out of the CNS to effector organs (muscles and glands).
3. Classification based on length
Depending upon the length of axons, neurons are divided into types:
1. Golgi type I
2. Golgi type II
1. Golgi type I
These neurons have long axons, the cell body of these neurons is located in the CNS and their
axons reach remote peripheral organs.
2. Golgi type II
This type of neurone possess short axons that does not send branches out of the grey matter of
the CNS.

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There are two types of motor neurons: somatic and autonomic. Somatic motor neurons are
responsible for both reflex and voluntary control of skeletal muscles. Autonomic motor
neurons innervate (send axons to) the involuntary effectors—smooth muscle, cardiac muscle,
and glands. The cell bodies of the autonomic neurons that innervate these organs are located
outside the CNS in autonomic ganglia. There are two subdivisions of autonomic neurons:
sympathetic and parasympathetic. Autonomic motor neurons, together with their central control
centers, constitute the autonomic nervous system.

NERVE AND CLASSIFICATION OF NERVES

A nerve is a bundle of axons located outside the CNS. In a nerve, the axons are arranged in
different bundles called fasciculi. The whole nerve is covered by tubular sheath, called
epineurium. Each fascicule is covered by perineurium and each nerve is fiber is covered by
endoneurium.

Figure 2: The structure and parts of a typical neuron

CLASSIFICATION OF NERVE FIBRES

The nerve fibres are classified by different methods. The basis of classification differs in each
method. They include:
1. Depending upon structure
2. Depending upon distribution
3. Depending upon origin

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 4. Depending upon function
5. Depending upon secretion of neurotransmitter
6. Depending upon diameter and conduction of impulse (Erlanger-Gasser classification)
1. Depending upon structure
Based on the structure, the nerve fibers are classified into two types.
 Myelinated Nerve fibers
Myelinated nerve fibers are the nerve fibers that are covered by myelin sheath
 Non-Myelinated Nerve fibers
Non-myelinated nerve fibers are the nerve fibers which are not covered by myelin sheath.
2. Depending upon distribution
The nerve fibers are divided into two types, on the basis of distribution
 Somatic nerve fibres
Somatic nerve fibres supply the skeletal muscles of the body
 Visceral or Autonomic nerve fibres
Autonomic nerve fibres supply the various internal/visceral organs.
3. Depending upon origin
On the basis of origin, nerve fibres are divided into two types
 Cranial nerves
Nerve fibers arising from the brain are called cranial nerves
 Spinal nerves
Nerve fibers arising from the spinal cord are called spinal nerves.
4. Depending upon function
Functionally, the nerve fibers are of two types:
 Sensory nerve fibers
The sensory nerve fibers carry sensory impulses from different parts of the body to the
central nervous system. These nerve fibers are also known as afferent nerve fibers.
 Motor neuron fibers
The motor nerve fibers carry motor impulses from central nervous system to different
parts of the body. These nerve fibers are also called the efferent nerve fibers.

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5. Depending upon the secretion of neurotransmitter
Depending upon the neurotransmitter substance secreted, the nerve fibers are divided into two
types.
 Adrenergic Nerve fibers
Adrenergic nerve fibers secrete noradrenaline.
 Cholinergic Nerve fibers
Cholinergic nerve fiber secrete acetylcholine
6. Depending upon diameter and conduction of impulse (Erlanger-Gasser classification)
Erlanger and Gasser classified the nerve fibers into three major types on the basis of diameter
(thickness) of the fibers and the rate of conduction of impulses.
 Type A nerve fibers
 Type B nerve fibers
 Type C nerve fibers

Table 1: Erlanger and Gasser classification of nerves

Type Diameter (µ) Velocity of conduction (m/s)
A alpha 12-24 70-120
A Beta 6-12 30-70
A Gamma 5-6 15-30
A delta 2-5 12-15
B 1-2 3-10
C < 1.5 0.5-2

Among these fibers, type A nerve fibers are the thickest fibers and type C nerve fibers are the
thinnest fibers.
The velocity of impulse through a nerve fiber is directly proportional to the thickness of the
fibers. The different types of nerve fibers along with diameter and velocity of conduction are
given in the table above.
Type A nerve fibers are divided into four types:
 Type A alpha nerve fibers
 Type A beta nerve fibers

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  Type A gamma nerve fibers
 Type A delta nerve fibers
Type A alpha fibers are also called the Type 1a fibers, Type A beta nerve fibers are called Type
II and Type A delta fibers are known as Type III fibers. The Type C fibers are also known as
Type IV fibers. All the nerve fibers are myelinated except C type of fibers,

PHYSIOLOGIC ANATOMY OF THE NERVE CELL (THE NEURONE)

The nervous system is composed of neurons, which produce and conduct electrochemical
impulses, and supporting cells, which assist the functions of neurons.
Neurons are the basic structural and functional units of the nervous system. They are specialized
to respond to physical and chemical stimuli, conduct electrochemical impulses, and release
chemical regulators. Through these activities, neurons enable the perception of sensory stimuli,
learning, memory, and the control of muscles and glands.
Supporting cells aid the functions of neurons and are about five times more abundant than
neurons. In the CNS, supporting cells are collectively called neuroglia, or simply glial cells (glia
= glue).
Neurons vary considerably in size and shape, they generally have four principal regions:
(1) a cell body,
(2) dendrites,
(3) an axon, and
(4) terminal boutons (buttons).
Dendrites and axons can be referred to generically as processes, or extensions from the cell
body.

Cell body (Soma)

The cell body is the enlarged portion of the neuron that contains the nucleus. It is the “nutritional
center” of the neuron where macromolecules are produced. The cell body also contains densely
staining areas of rough endoplasmic reticulum known as Nissl bodies that are not found in the
dendrites or axon. The cell bodies within the CNS are frequently clustered into groups called
nuclei (not to be confused with the nucleus of a cell). Cell bodies in the PNS usually occur in
clusters called ganglia.

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Dendrites
Dendrites (dendron = tree branch) are thin, branched processes that extend from the cytoplasm
of the cell body. Dendrites provide a receptive area that transmits electrical impulses to the cell
body.
Axon
The axon is a longer process than the dendrites, that conducts impulses away from the cell body.
The origin of the axon near the cell body is an expanded region called the axon hillock; which is
important because it is site for the generation of action potential or nerve impulses.
Proteins and other molecules are transported through the axon at faster rates than could be
achieved by simple diffusion. This rapid movement is produced by two different mechanisms:
axoplasmic flow and axonal transport. Axoplasmic flow, the slower of the two, results from
rhythmic waves of contraction that push the cytoplasm from the axon hillock to the nerve
endings. Axonal transport, which employs microtubules and is more rapid and more selective,
may occur in a retrograde (towards the cell body) direction as well as in a forward/orthograde
direction (towards the synaptic terminal/terminal buttons). Retrograde transport may be
responsible for the movement of herpes virus, rabies virus, and tetanus toxin from the nerve
terminals into cell bodies.

Neurilemma and Myelin Sheath

All axons in the PNS (myelinated and unmyelinated) are surrounded by a continuous, living
sheath of Schwann cells, known as the neurilemma, or sheath of Schwann. The axons of the
CNS, by contrast, lack a neurilemma (Schwann cells are only found in the PNS). Some axons in
the PNS and CNS are surrounded by a myelin sheath. In the PNS, this insulating covering is
formed by successive wrappings of the cell membrane of Schwann cells but in the CNS, it is
formed by oligodendrocytes.
Those axons smaller than 2 micrometers (2 μm) in diameter are usually unmyelinated (have no
myelin sheath), whereas those that are larger are likely to be myelinated. Myelinated axons
conduct impulses more rapidly than those that are unmyelinated.

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Myelin Sheath in PNS
In the process of myelin formation in the PNS, Schwann cells roll around the axon, much like a
roll of electrician’s tape is wrapped around a wire. Unlike electrician’s tape, however, the
Schwann cell wrappings are made in the same spot, so that each wrapping overlaps the previous
layers. The cytoplasm, meanwhile, is forced into the outer region of the Schwann cell, much as
toothpaste is squeezed to the top of the tube as the bottom is rolled up. Each Schwann cell wraps
only about a millimeter of axon, leaving gaps of exposed axon between the adjacent Schwann
cells. These gaps in the myelin sheath are known as the nodes of Ranvier. The successive
wrappings of Schwann cell membrane provide insulation around the axon, leaving only the
nodes of Ranvier exposed to produce nerve impulses. The Schwann cells remain alive as their
cytoplasm is forced to the outside of the myelin sheath. As a result, myelinated axons of the PNS
are surrounded by a living sheath of Schwann cells, or neurilemma. Unmyelinated axons are also
surrounded by a neurilemma, but they differ from myelinated axons in that they lack the multiple
wrappings of Schwann cell plasma membrane that comprise the myelin sheath.

Myelin Sheath in CNS

The myelin sheaths of the CNS are formed by oligodendrocytes. The myelin sheaths around
axons of the CNS give this tissue a white color; areas of the CNS that contain a high
concentration of axons thus form the white matter. The gray matter of the CNS is composed of
high concentrations of cell bodies and dendrites, which lack myelin sheaths.

Terminal boutons(buttons)/Synaptic terminals

The terminal buttons/Synaptic terminals are the site of release of neurotransmitters and are
usually close to another neurone or effector cell.

GLIAL CELLS (SUPPORTING CELLS/NEUROGLIAL)

Glial cells help support, connect, and protect the neurons of the central and peripheral nervous
systems. They come in many shapes, sizes, and types, each performing specialized functions. In
the CNS, glial cells regulate neurotransmission and help form the blood-brain barrier. They also
clean up dead neurons, synchronize nerve impulses, and regulate brain metabolism.

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In the PNS, Schwann cells create a myelin sheath for faster conduction. Additionally, satellite
cells provide nutritional support for neurons.
There are two types of supporting cells in the peripheral nervous system:
1. Schwann cells, which form myelin sheaths around peripheral axons; and
2. Satellite cells, or ganglionic gliocytes, which support neuron cells bodies within the ganglia
of the PNS.
There are four types of supporting cells, called neuroglial (or glial) cells, in the central nervous
system:
1. Oligodendrocytes, which form myelin sheaths around axons of the CNS;
2. Microglia, which migrate through the CNS and phagocytose foreign and degenerated
material;
3. Astrocytes, which help to regulate the external environment of neurons in the CNS; and
4. Ependymal cells, which line the ventricles (cavities) of thebrain and the central canal of the
spinal cord.

Neurotrophins
Chemicals called neurotrophins helps promote neuron growth. Nerve growth factor (NGF) was
the first neurotrophin to be identified; others include brain-derived neurotrophic factor (BDNF);
glial-derived neurotrophic factor (GDNF); neurotrophin-3; and neurotrophin-4/5 (the number
depends on the species). NGF and neurotrophin-3 are known to be particularly important in the
embryonic development of sensory neurons and sympathetic ganglia. Neurotrophins also have
important functions in the adult nervous system, they have the following functions.
 Maintenance of sympathetic ganglia,
 Maturation of sensory neurons
 Maintenance of spinal motor neurons and
 Sustenance of neurons in the brain that uses the chemical dopamine as a neurotransmitter.
 Promotion of neuronal growth

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ELECTRICAL ACTIVITY OF THE AXON
The existence of ‘‘animal electricity’’ had been known for more than 200 years, but the first
direct experimental evidence for it was not provided until the development of electronic
amplifiers and oscilloscopes.
A central aspect of the physiology of neurons and muscle cells is their ability to produce and
conduct these changes in membrane potential. Such an ability is termed excitability or
irritability.

Resting membrane potential (RMP)

Resting membrane potential is the electrical potential difference (voltage) across the cell
membrane (between inside and outside of the cell) under resting conditions. It is also referred to
as membrane potential, transmembrane potential, transmembrane potential difference or
transmembrane potential gradient.
All cells in the body maintain a potential difference (voltage) across the membrane, or resting
membrane potential, in which the inside of the cell is negatively charged in comparison to the
outside of the cell (for example, in neurons it is –70 mV).

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IONIC BASIS OF RESTING MEMBRANE POTENTIAL
The development and maintenance of resting membrane potential in a muscle fiber or a neurone
are carried out by some mechanisms, which produce ionic imbalance across the cell membrane.
This results in the development of more positivity outside and more negative inside the cell
(potential difference).
This potential difference is largely the result of
1. The permeability properties of the plasma membrane. The membrane traps large,
negatively charged organic molecules within the cell and permits only limited diffusion of
positively charged inorganic ions. These properties result in an unequal distribution of these ions
across the membrane.
2. The action of the Na+/K+ pump also helps to maintain a potential difference because they
pump out three sodium ions (Na+) for every two potassium ions (K+) that they transport into the
cell. Partly as a result of these pumps, Na + is more highly concentrated in the extracellular fluid
than inside the cell (ICF), whereas K + is more highly concentrated within the cell (ICF) than the
ECF.
3. Leak channels
The ion of three important ions; sodium, chloride and potassium also play an important role in
maintaining the resting membrane potential. These ions are unequally distributed across the cell
membrane. The sodium and chloride ions are more outside and potassium are more inside. Since
the chloride channels are mostly closed in resting conditions these ions are retained outside the
cell. Thus, only positive ions, sodium and potassium ions can move across the cell membrane.
The sodium is actively transported against concentration gradient out of the cell and potassium is
actively transported against the concentration into the cell. However, because of the
concentration gradient, sodium ion diffuses back into the cell through sodium leak channels and
potassium diffuses out of the cell through potassium leak channels.
In resting conditions, almost all the potassium channels are open but most of the sodium leak
channels are closed. Because of this, potassium ion which is transported actively into the cell can
diffuse back out of the cell in an attempt to maintain the concentration equilibrium. But only
very little amount of sodium transported actively out of the cell can diffuse back into the cell.
This means in resting conditions, the passive potassium efflux is much greater than the passive
sodium influx. It helps in establishing and maintaining the resting membrane potential.

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After establishment of the resting potential membrane potential, the efflux of potassium ions
stops in spite of concentration gradient.
This occurs because of two reasons
1. The positivity outside the cell repels the positive potassium and prevents the further
efflux of these ions.
2. The negativity inside the cell attracts the positive potassium ions and prevents further
leakage of these ions outside.
Importance of intracellular potassium ions
The concentration of potassium ions inside the cell is about 140 mEq/L. It is almost equal to that
of sodium outside. The high concentration of potassium inside the cell is essential to check the
negativity. Normally the negativity of (resting membrane potential) inside the muscle fibres is
-90 mV and in nerve fibre is -70mV. It is because of the presence of negativity charged proteins,
organic phosphates and sulfates which cannot move out normally. Suppose if the potassium ion
is not present or decreases, the negativity increases beyond -120mV, which is called
hyperpolarization. At this stage the development of action potential is either infinitely delayed or
does not occur.

ACTION POTENTIAL
Conduction of nerve signals is done by a rapid membrane depolarization that changes the normal
resting negative potential to a positive potential. This is followed by a repolarization back to the
normal negative membrane potential. These phenomena is defined as action potential.
An action potential is also defined as a wave of electrical discharge that travels along the
membrane.
Action potential occurs in two phases:
1. Depolarization and
2. Repolarization

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Depolarization.
When the impulse reaches the nerve, the polarized condition (-70mV). The interior of the nerve
fibre becomes more positive and the outside becomes more negative i.e the polarized state is
abolished. This condition is called depolarization.
Repolarization
Within a short time, the potential returns to the resting membrane potential the interior of nerve
becomes more negative than the exterior. So the polarized state of the nerve is re-established.
This is known as repolarization.

ACTION POTENTIAL IN NERVE

Action potential in a nerve fiber is similar to that in a muscle, except for some minor differences.
Resting membrane potential in the nerve fiber is –70 mV. The firing level is at –55 mV.
Depolarization ends at +35 mV. Usually, the action potential starts in the initial segment of nerve
fiber.

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Figure 3: An Action potential curve

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ACTION POTENTIAL IN SKELETAL MUSCLE
Action potential curve is the graphical registration of electrical activity that occurs in an
excitable tissue such as skeletal muscle after stimulation. It shows three major parts:
1. Latent period
2. Depolarization
3. Repolarization.
Resting membrane potential in skeletal muscle is –90 mV and it is recorded as a straight
baseline.
1. Latent period
The stimulus artifact is followed by a short period without any change. This period is called
latent period.
2. Firing level and Depolarization
Depolarization starts after the latent period, it is initially very slow. After the initial slow
depolarization, the rate of depolarization increases suddenly. The point at which the rate of
depolarization increases is called firing level.
Overshoot
From the firing level the curve reaches the isoelectric potential (zero potential) rapidly and then
overshoots beyond the zero potential upto +55mV.
3. Repolarization
When depolarization is completed (+55mV), the repolarization starts. Initially it occurs rapidly
and then it becomes slow.
Spike potential
The rapid rise in depolarization and the rapid fall in repolarization are together called spike
potential.
After depolarization or negative after potential
The rapid fall in repolarization is followed by a slow repolarization process. It is called after
depolarization or negative after potential.
After hyperpolarization or positive after potential
After reaching the resting membrane potential (-90mv) it becomes more negative than resting
level. This is called after hyperpolarization or positive after potential. This lasts for more than
50 milliseconds. After this, the normal resting membrane potential is restored.

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IONIC BASIS OF ACTION POTENTIAL
The action potential begins with depolarization of the membrane in response to a stimulus. This
initial depolarization opens voltage-gated sodium channels, which increases the membrane
permeability to sodium ions several hundredfold . This allows more sodium ions to move into the
cell, and the cell becomes more and more depolarized until a threshold is reached to trigger the
action potential. This is called the threshold potential. After the threshold potential is reached,
more voltage-gated sodium channels open.
The membrane potential overshoots, becoming positive on the inside and negative on the outside
of the membrane. At the peak of the action potential, sodium permeability abruptly decreases and
voltage-gated potassium channels open. The membrane begins to rapidly repolarize to its resting
level.
Closure of the sodium channels alone would restore the membrane potential to its resting level
since potassium efflux would then exceed sodium influx. However, the process is speeded up by
the simultaneous increase in potassium permeability. Potassium diffusion out of the cell becomes
much greater than the sodium diffusion into the cell, rapidly returning the membrane potential to
its resting level. In fact, after the sodium channels have closed, some of the voltage-gated
potassium channels are still open, and in nerve cells there is generally a small hyperpolarization
of the membrane potential beyond the resting level called the afterhyperpolarization. Once the
voltage-gated potassium channels close, the resting membrane potential is restored. Chloride
permeability does not change during the action potential.

All-or-None Law
Once a region of axon membrane has been depolarized to a threshold value, the positive
feedback effect, leads to increased Na permeability causing more depolarization and the
membrane potential to shoot toward about +30 mV.
The amplitude (size) of action potentials is therefore all or none. When depolarization is below
a threshold value, the voltage regulated gates are closed; when depolarization reaches threshold,
a maximum potential change (the action potential) is produced and propagated.

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Threshold and Graded potential
The potential change produced when threshold is reached is known as the action potential, which
is elicited in an all-or-none fashion. Stimuli below threshold (Subthreshold potentials) fail to
elicit an action potential and are referred to as electrotonic potentials or graded potential;
stimuli at threshold or above threshold successfully produce an action potential.

Figure 4: Difference between action potential and graded potential

REFRACTORY PERIODS IN SKELETAL MUSCLE

Absolute Refractory Period
The absolute refractory period is that period during which no matter how strong the stimulus, it
cannot induce a second action potential.
Relative Refractory Period
The relative refractory period is that period during which a greater than normal stimulus is
required to induce a second action potential.

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 MUSCLE PHYSIOLOGY

CLASSIFICATION OF MUSCLES
Human body has more than 600 muscles. Muscles perform many useful functions and help us in
doing everything in day-to-day life. Muscles are classified by three different methods, based on
different factors:
I. Depending upon the presence or absence of striations
II. Depending upon the control
III. Depending upon the situation.
I. DEPENDING UPON STRIATIONS
Depending upon the presence or absence of cross striations, the muscles are divided into two
groups:
1. Striated muscle
2. Non-striated muscle.
1. Striated Muscle
Striated muscle is the muscle which has a large number of cross-striations (transverse lines).
Skeletal muscle and cardiac muscle belong to this category.
2. Non-striated Muscle
Muscle which does not have cross-striations is called non-striated muscle. It is also called plain
muscle or smooth muscle. It is found in the wall of the visceral organs.
„
II. DEPENDING UPON CONTROL
Depending upon control, the muscles are classified into two types:
1. Voluntary muscle
2. Involuntary muscle.
1. Voluntary Muscle
Voluntary muscle is the muscle that is controlled by the will. Skeletal muscles are the voluntary
muscles. These muscles are innervated by somatic nerves.
2. Involuntary Muscle
Muscle that cannot be controlled by will is called involuntary muscle. Cardiac muscle and
smooth muscle are involuntary muscles. These muscles are innervated by autonomic nerves.

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III. DEPENDING UPON LOCATION
Depending upon location, the muscles are classified into three types:
1. Skeletal muscle
2. Cardiac muscle
3. Smooth muscle.

1. Skeletal Muscle
Skeletal muscle is situated in association with bones forming the skeletal system. The skeletal
muscles form 40% to 50% of body mass and are voluntary and striated. These muscles are
supplied by somatic nerves. Fibers of the skeletal muscles are arranged in parallel. In most of the
skeletal muscles, muscle fibers are attached to tendons on either end. Skeletal muscles are
anchored to the bones by the tendons.
2. Cardiac Muscle
Cardiac muscle forms the musculature of the heart. These muscles are striated and involuntary.
Cardiac muscles are supplied by autonomic nerve fibers.
3. Smooth Muscle
Smooth muscle is situated in association with viscera. It is also called visceral muscle. It is
different from skeletal and cardiac muscles because of the absence of cross striations, hence the
name smooth muscle. Smooth muscle is supplied by autonomic nerve fibers. Smooth muscles
form the main contractile units of wall of the various visceral organs.

SKELETAL MUSCLE
The skeletal muscle cells are long, slender and cylindrical in shape. The muscle fibres are
multinucleated and arranged parallel to one another with connective tissue in between. The
muscle mass is separated from the neighbouring tissues by the thick fibrous tissue layer known
as fascia. Beneath the fascia, the muscle is covered by a connective tissue sheath called
epimysium. In the muscle, the muscle fibres are arranged in various groups called the bundles
or fasciculi. The connective tissue sheath that covers each fascicule is called perimysium. Each
muscle fibre is covered by the connective tissue called endomysium.

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The muscle fibres are attached to a tough cord or connective tissue called tendon. Tendon is in
turn attached to the bone. The tendon of some muscles is thin, flat and stretched but tough. Such
type of tendon is called aponeurosis.
The muscle fibre is enclosed by a cell membrane called plasma membrane that lies beneath the
endomysium. It is also called the sarcolemma. The cytoplasm of the muscle is known as
sarcoplasm. Many structures are embedded within the sarcoplasm.
1. Nuclei
2. Myofibril
3. Golgi apparatus
4. Mitochondria
5. Sarcoplasmic reticulum
6. Ribosomes
7. Myoglobin
All the organelles of muscle fibres have the same function as those of other cells.

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Figure: Structure of the skeletal muscle

MYOFIBRIL
Myofibrils are the fine parallel filaments present in sarcoplasm of the muscle cell. The myofibrils
run through the entire length of the muscle fibre.

Ultrastructure of the myofibrils

Light microscopic studies show that each myofibril consist of two alternating bands namely

 Light band or I band

 Dark band or A band

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In an intact muscle fibre I and A band of the adjacent myofibrils are placed side by side. It gives
the appearance of characteristics cross striations in the muscle fibre.

A narrow lighter area called a H zone is seen at the middle of the A band. The I band is divided
into two portions by a narrow dark line called a Z line. The portion of myofibril in between two
Z line is called sarcomere.

Sarcomere
The sarcomere is the structural and functional unit of the skeletal muscle. It is called the basic
contractile unit of the muscle. Each sarcomere extends between two Z lines of myofibril. Thus,
each myofibril contains many sarcomeres arranged in series throughout its length. Each
myofibril consists of alternate dark A band, between the A band, there is an area called H zone.
In the middle of the H zone lies the middle part of myosin filament. This called M line. Similarly
the light I band is divided into two equal parts by a narrow line called Z line.

Ultrastructure of Myofibrils
Muscle cell contains many parallel myofibrils have DARK bands (A bands) and LIGHT bands (I
bands) that cause the "striated" appearance of muscle. A band and I band result from the
arrangement of overlapping and non-overlapping regions of two types of myofilaments.

 Thick filaments (Myosin)

 Thin filaments (Actin)

CONTRACTILE PROTEINS MUSCLE

The Myosin filament

The thick filament consititute the myosin filament and the myosin filament are made of myosin
molecules. Each myosin filament consist of about 200 myosin molecules. Myosin is a globulin
with a molecular weight of 480 000. Each molecule is made up of 6 polypeptides chains of
which two are heavy chains. The two heavy chains twist around each other to form a double
helix This part of the heavy chain forms the tail portion of the myosin molecule. At one end the
two chains remain twisted around one another whereas at the other end both the chains turn away

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in opposite directions and form the globular head portion. To each of this head are attached two
light chain thus there are four light chains in each myosin molecule. Each myosin head has two
attachment sites. One site is for actin filament and the other one is for one a ATP molecule. In
the central part of the myosin filament, which is called the H zone the myosin head is absent.

Actin Filament
The actin molecules are the major constituents of the thin actin filaments, others being the
tropomyosin and troponins. There are about 300 to 400 actin molecules in each actin filament.
The molecular weight of each molecule is 42,000. The actin molecule in the actin filament are
also arranged in the form of a double helix. Each actin molecule has an active site to which the
myosin head is attached.
Tropomyosin
There about 40 to 60 tropomyosin molecules situated along the double helix strand of actin
filament. Each tropomyosin molecule has the molecular weight of 70,000. When the muscle is
relaxed, the tropomyosin molecules cover all the active sites of actin molecules.
Troponin
It is formed by three subunits
Troponin I: attached to actin
Troponin T: attached to tropmyosin
Troponin C: attached to calcium ions

Other proteins found in the sarcomere of the muscle include actinin, desmin, nebulin, titin.

SARCOTUBULAR SYSTEM
The sarcotubular system is formed mainly by two structures
 Transverse or T tubules
 Longitudinal or L tubules.

T tubules
The T tubules are narrow tubules formed by the invagination of the sarcolemma. These tubules
penetrate all the way from one side of the muscle to the other. Because of their origin from the

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sarcolemma the tube opens to the exterior of the muscle cell. Therefore, the ECF run through
their lumen.

L tubules
The L tubule is network of membranous channels that surrounds each myofibril and runs parallel
to it. It formed by the sarcoplasmic reticulum. These tubules run in long axes of the muscle fibre
hence the name longitudinal tubules. L tubules formed a closed tubular system around each
myofibril and do not open to the exterior like the T tubules. The L tubules corresponds to the
endoplasmic reticulum in other cells. At regular intervals throughout the length of the myofibrils,
the L tubules dilate to form a pair of lateral sacs called terminal cisternae. Each pair of cisternae
is in close contact with T tubule. The T tubule along with the cisternae on either side is called the
triad of the skeletal muscles.

Functions of the Sarcotubular systems

Function of T tubules
T tubules are responsible for rapid transmission of impulse in the form of action potential from
sarcolemma to the myofibrils. When muscle is stimulated, the action potential develops in
sarcolemma and spreads through it. Since T tubule are the continuation of the sarcolemma, the
action potential passes through them and reaches the interior of the muscle fibre rapidly.

Function of L tubules
The L tubules are responsible for the storage of large quantities of calcium ions. When the action
potential reaches the cisternae of the L tubule, the calcium are released into the sarcoplasm. The
calcium ion triggers the processes involved in contraction of the muscle.

MOLECULAR BASIS OF MUSCULAR CONTRACTION

Excitation-Contraction Coupling
Excitation-contraction coupling refers to the sequence of events by which an action potential in
the plasma membrane of a muscle fiber leads muscle contraction. The skeletal muscle plasma
membrane is an excitable membrane capable of generating and propagating action potentials.

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The action potential in the plasma membrane does not directly act upon the contractile proteins
but instead produces a state of increased cytosolic calcium concentration, which continues to
activate the contractile apparatus. When an action potential is transmitted along the sarcolemma
of the muscle fiber and then down the T-tubules, Ca 2+ is released from the terminal cisternae of
the sarcoplamic reitculum (SR) into the myoplasm. This release of Ca 2+ from the SR raises the
intracellular Ca2+ concentration, which in turn promotes actin-myosin interaction and contraction.

The mechanism by which Ca2+ promotes contraction as follows. Ca2+ released from the SR binds
to troponin-C. Once bound with Ca 2+, troponin-C facilitates the movement of the tropomyosin
molecule toward the actin filament. This movement of tropomyosin exposes the myosin-binding
site on the actin filament, allowing a cross-bridge to form (sliding of thin filament over the thick
filament), and thereby causing contraction of the muscle. Once myosin and actin have bound,
ATP-dependent conformational changes in the myosin molecule result in the movement of the
actin filaments toward the center of the sarcomere. This shortens the length of the sarcomere, and
thereby contracts the muscle fiber.

Summary of Biochemical Events of Muscle Contraction

1. Nerve impulse arrives at neuromuscular junction (neuron to muscle cell communication).
2. Acetylcholine (ACh) is released from motor neuron and diffuses across to the motor end
plate.
3. ACh binds with nicotinic receptors at the motor end plate (a specialized portion of
sarcolemma). Receptors are linked to ligand gated ion channels, allowing Na+ influx (plus a
little bit of K+ efflux), resulting in the depolarization of the muscle cell membrane. This
results in a motor end plate potential, which becomes an action potential (AP) in muscle
cells.
4. The impulse (AP) is spread very quickly throughout the cell by the transverse ("T") tubules.
The AP traveling down the t-tubules, opens gates on the SR. This then causes the SR to
release the Ca2+ it has stored there into the cytosol (sarcoplasm) of the skeletal muscle.
5. The increase in Ca2+ binds to the regulatory protein troponin C, causing it to change shape
and move.

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 6. The movement of troponin then moves tropomyosin away from covering the active site on
actin, thus exposing the myosin binding site on actin.
7. Due to the strong affinity between them, the myosin head binds to the actin (crossbridge).
8. Crossbridge formation stimulates ATPase activity, and allows the power stroke to occur.
The power stroke is the 'pulling' of actin toward the M line.
9. This muscle contraction will continue until: 1) the impulse stops or 2) fatigue occurs.
If Nerve Impulse Stops:
1. Ca2+ will be pumped back into SR by active transport (Ca2+ATPase).
2. Without the increased [Ca2+]i, troponin is no longer bound to Ca2+ and the tropomyosin then
moves back over to cover the binding sites on actin. Thus crossbridges formation cannot
occur.
When all the myosin heads detach, actin slides back to its original position and the muscle
relaxes.

NEUROMUSCULAR TRANSMISSION: THE NEUROMUSCULAR JUNCTION

(MYONEURAL JUNCTION)

The synapse between the axons of a motor neuron and a skeletal fiber is called the
Neuromuscular junction.

Anatomy
As the axon supplying a skeletal muscle fiber approaches its termination, it loses its myelin
sheath and divides into a number of terminal boutons, or endfeet. The endfeet contain many
small, clear vesicles that contain acetylcholine, the transmitter at these junctions. The endings fit
into junctional folds, which are depressions in the motor end plate, the thickened portion of the
muscle membrane at the junction. The space between the nerve and the thickened muscle
membrane is called the synaptic cleft. The whole structure is known as the neuromuscular, or
myoneural junction. Only one nerve fiber ends on each end plate, with no convergence of
multiple inputs.

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Figure 7: Neuromuscular Junction

Sequence of events during neuromuscular transmission

The events occurring during transmission of impulses from the motor nerve to the muscle are
somewhat similar to those occurring at neuron-to-neuron synapses. The impulse arriving in the
end of the motor neuron increases the permeability of its endings to Ca2+. Ca2+ enters the endings
and triggers a marked increase in exocytosis of the acetylcholine-containing vesicles. The
acetylcholine diffuses to the muscle-type nicotinic acetylcholine receptors, which are
concentrated at the tops of the junctional folds of the membrane of the motor end plate. Binding
of acetylcholine to these receptors increases the Na+ and K+ conductance of the membrane, and
the resultant influx of Na+ produces a depolarizing potential, is called the end plate potential.
The current sink created by this local potential depolarizes the adjacent muscle membrane to its
firing level. Acetylcholine is then removed from the synaptic cleft by acetylcholinesterase, which
is present in high concentration at the neuromuscular junction. The muscle action potential, in
turn, initiates muscle contraction, as described previously.

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Figure: Sequence of neuromuscular transmission

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Figure: Neuromuscular transmission: sequence of events
NEUROMUSCULAR BLOCKERS
Neuromuscular blockers are the drugs, which prevent transmission of impulses from nerve fiber
to the muscle fiber through the neuromuscular junctions. These drugs are used widely during
surgery and trauma care. Neuromuscular blockers used during anesthesia relax the skeletal
muscles and induce paralysis so that surgery can be conducted with less complication.
The following are important neuromuscular blockers, which are commonly used in clinics and
research.
1. Curare
Curare prevents the neuromuscular transmission by combining with acetylcholine receptors. So,
the acetylcholine cannot combine with the receptors. And, the endplate potential cannot develop.

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Since curare blocks the neuromuscular transmission by acting on the acetylcholine receptors, it is
called receptor blocker.
2. Bungarotoxin
Bungarotoxin is a toxin from the venom of deadly snakes. It affects the neuromuscular
transmission by blocking the acetylcholine receptors.
3. Succinylcholine and Carbamylcholine
These drugs block the neuromuscular transmission by acting like acetylcholine and keeping the
muscle in a depolarized state. But, these drugs are not destroyed by acetylholinesterase. So, the
muscle remains in a depolarized state for a long time.
4. Botulinum Toxin
Botulinum toxin is derived from the bacteria Clostridium botulinum. It prevents release of
acetylcholine from axon terminal into the neuromuscular junction.

DRUGS STIMULATING NEUROMUSCULAR JUNCTION

Neuromuscular junction can be stimulated by some drugs like neostigmine, physostigmine and
diisopropyl fluorophosphate. These drugs inactivate the enzyme, acetyl cholinesterase. So, the
acetylcholine is not hydrolyzed. It leads to repeated stimulation and continuous contraction of the
muscle.

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DISORDERS OF NMJ
Myasthenia Gravis
Myasthenia gravis is a serious and sometimes fatal disease in which skeletal muscles are weak
and tire easily. It is caused by the formation of circulating antibodies to the muscle type of
nicotinic acetylcholine receptors. These antibodies destroy some of the receptors. In
myasthenia gravis, neuromuscular transmission fails at these low levels of quantal release.
This leads to the major clinical feature of the disease– muscle fatigue with sustained or repeated
activity. Weakness improves after a period of rest or after administration of acetylcholinesterase
inhibitors. Cholinesterase inhibitors prevent metabolism of acetylcholine and can thus
compensate for the normal decline in released neurotransmitters during repeated stimulation.

Lambert–Eaton Syndrome
Another condition that resembles myasthenia gravis is the relatively rare condition called
Lambert–Eaton Syndrome (LEMS). In this condition, muscle weakness is caused by an
autoimmune attack against one of the Ca2+ channels in the nerve endings at the neuromuscular
junction. This decreases the normal Ca 2+ influx that causes acetylcholine release. Repetitive
stimulation of the motor nerve facilitates accumulation of Ca 2+ in the nerve terminal and
increases acetylcholine release, leading to an increase in muscle strength. This is in contrast to
myasthenia gravis in which patients are fatigued by repetitive stimulation. About 40% of patients
with LEMS also have cancer, especially cancer of the lung. One theory is that antibodies that
have been produced to attack the cancer cells may also attack Ca 2+ channels, leading to LEMS.
LEMS has also been associated with cancer of the breast, stomach, colon, prostate, bladder,
kidney, or gall bladder.

SMOOTH MUSCLE
Smooth muscles are non-striated (plain) and involuntary muscles. These muscles are present in
almost all the organs in the form of sheets, bundles or sheaths around other tissues. Smooth
muscles form the major contractile tissues of various organs. Structures in which smooth muscle
fibers are present:
1. Wall of organs like esophagus, stomach and intestine in the gastrointestinal tract

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2. Ducts of digestive glands
3. Trachea, bronchial tube and alveolar ducts of respiratory tract
4. Ureter, urinary bladder and urethra in excretory system
5. Wall of the blood vessels in circulatory system
6. Errector pilorum of skin
7. Mammary glands, uterus, genital ducts, prostate gland and scrotum in the reproductive system
8. Iris and ciliary body of the eye.

STRUCTURE OF SMOOTH MUSCLE

Smooth muscle fibers are fusiform or elongated cells. These fibers are generally very small,
measuring 2 to 5 microns in diameter and 50 to 200 microns in length. Nucleus is single and
elongated and it is centrally placed. Normally, two or more nucleoli are present in the nucleus.
Myofibrils and Sarcomere
Well-defined myofibrils and sarcomere are absent in smooth muscles. So the alternate dark and
light bands are absent. Absence of dark and light bands gives the non-striated appearance to the
smooth muscle, although actin and myosin are present.
Myofilaments and Contractile Proteins
Contractile proteins in smooth muscle fiber are actin, myosin and tropomyosin. But troponin or
troponin-like substance is absent.
Thick and thin filaments are present in smooth muscle. However, these filaments are not
arranged in orderly fashion as in skeletal muscle. Thick filaments are formed by myosin
molecules and are scattered in sarcoplasm. These thick filaments contain a greater number of
cross bridges than in skeletal muscle. Thin filaments are formed by actin and tropomyosin
molecules.

Covering and Tendons

Smooth muscle fibers are covered by connective tissue. But the tendons and aponeurosis are
absent.
Sarcotubular System

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Sarcotubular system in smooth muscle fibers is in the form of network. ‘T’ tubules are absent
and ‘L’ tubules are poorly developed.

TYPES OF SMOOTH MUSCLE FIBERS

Smooth muscle has been subdivided into two groups: single-unit and multiunit.
1. Single-unit or visceral smooth muscle fibers
2. Multiunit smooth muscle fibers.
Single-Unit or Visceral Smooth Muscle Fibers
Single-unit smooth muscle fibers possess interconnecting gap junctions. The gap junctions allow
rapid spread of action potential throughout the tissue so that all the muscle fibers show
synchronous contraction as a single unit. Single unit smooth muscle fibers are also called
visceral smooth muscle fibers.
Features of single-unit smooth muscle fibers:
1. Muscle fibers are arranged in sheets or bundles
2. Cell membrane of adjacent fibers fuses at many points to form gap junctions. Through the gap
junctions, ions move freely from one cell to the other. Thus a functional syncytium is
developed. The syncytium contracts as a single unit. In this way, the visceral smooth muscle
resembles cardiac muscle more than the skeletal muscle.
Distribution of Single-unit Smooth Muscle Fibers
Visceral smooth muscle fibers are found in the walls of the organs such as gastrointestinal
organs, uterus, ureters, respiratory tract, etc.

Multiunit Smooth Muscle Fibers

Multiunit smooth muscle fibers are the muscle fibers without interconnecting gap junctions.
These smooth muscle fibers resemble the skeletal muscle fibers in many ways.

Features of multiunit smooth muscle fibers:

1. Muscle fibers are individual fibers
2. Each muscle fiber is innervated by a single nerve ending

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3. Each muscle fiber has got an outer membrane made up of glycoprotein, which helps to
insulate and separate the muscle fibers from one another
4. Control of these muscle fibers is mainly by nerve signals
5. These smooth muscle fibers do not exhibit spontaneous contractions.

Distribution of Multiunit Smooth Muscle Fibers

Multiunit muscle fibers are in ciliary muscles of the eye, iris of the eye, nictitating membrane
(in cat), errector pili and smooth muscles of the blood vessels and urinary bladder.

ELECTRICAL ACTIVITY IN SINGLE-UNIT SMOOTH MUSCLE

Usually 30 to 40 smooth muscle fibers are simultaneously depolarized, which leads to
development of self propagating action potential. It is possible because of gap junctions and
syncytial arrangements of single-unit smooth muscles. of 10 to 15 mV . The cause of the slow-
wave rhythm is not known. It is suggested that it may be due to the rhythmic modulations in the
activities of sodium potassium pump. The slow wave is not action potential and it cannot cause
contraction of the muscle. But it initiates the action potential.

IONIC BASIS OF ACTION POTENTIAL

The important difference between action potential in skeletal muscle and smooth muscle lies in
the ionic basis of depolarization. In skeletal muscle, the depolarization occurs due to opening of
sodium channels and entry of sodium ions from extracellular fluid into the muscle fiber. But in
smooth muscle, the depolarization is due to entry of calcium ions rather than sodium ions. Unlike
the fast sodium channels, the calcium channels open and close slowly. It is responsible for the
prolonged action potential with plateau in smooth muscles. The calcium ions play an important
role during the contraction of the muscle.

Contractile Apparatus of smooth muscles

Compared to skeletal muscles, in smooth muscles, the contraction and relaxation processes are
slow. The latent period is also long. Thus, the total twitch period is very long and it is about 1 to
3 seconds. In skeletal muscle, the total twitch period is 0.1 sec. The thin filaments of smooth
muscle have an actin and tropomyosin composition and structure similar to skeletal muscle.

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However, the cellular content of actin and tropomyosin in smooth muscle is about twice that of
striated muscle. Smooth muscle lacks troponin and nebulin, but contains two proteins not found
in striated muscle: caldesmon and calponin. The precise roles of these proteins are unknown,

Molecular Basis of Smooth Muscle Contraction (Excitation contraction coupling in Smooth

muscle)
The process of excitation and contraction is very slow in smooth muscles because of poor
development of ‘L’ tubules (sarcoplasmic reticulum). So, the calcium ions, which are responsible
for excitation-contraction coupling, must be obtained from the extracellular fluid. It makes the
process of excitation-contraction coupling slow.

Stimulation of ATPase activity of myosin in smooth muscle is different from that in the skeletal
muscle. In smooth muscle, the myosin has to be phosphorylated for the activation of myosin
ATPase. Phosphorylation of myosin occurs in the following manner:
1. Calcium, which enters the sarcoplasm from the extracellular fluid combines with a protein
called calmodulin and forms calcium-calmodulin complex.
2. It activates calmodulin-dependent myosin light chain kinase.
3. This enzyme in turn causes phosphorylation of myosin followed by activation of myosin
ATPase.
4. Now, the sliding of actin filaments starts. Phosphorylated myosin gets attached to the actin
molecule for longer period. It is called latch-bridge mechanism and it is responsible for the
sustained contraction of the muscle with expenditure of little energy.

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 Figure 5: Summary of excitation contraction coupling in Smooth muscle

CARDIAC MUSCLE
Cardiac muscle combines properties of both skeletal and smooth muscle. The cells are striated
as the result of an arrangement of thick myosin and thin actin filaments similar to that of skeletal
muscle. Cardiac muscle cells are considerably shorter than skeletal muscle fibers, however, and
have several branching processes. Adjacent cells are joined end to end at structures called
intercalated disks.
Heart is made up of three layers of tissues: outer pericardium, middle myocardium and the inner
endocardium. The Myocardium is the middle layer of wall of the heart and it is formed by
cardiac muscle fibers or cardiac myocytes. Myocardium forms the bulk of the heart and it is
responsible for pumping action of the heart. Unlike skeletal muscle fibers, the cardiac muscle
fibers are involuntary in nature.
Myocardium has three types of muscle fibers:
i. Muscle fibers which form contractile unit of heart

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ii. Muscle fibers which form pacemaker
iii. Muscle fibers which form conductive system.

Muscle Fibers which form Contractile Unit of Heart

These cardiac muscle fibers are striated and resemble the skeletal muscle fibers in structure.
Cardiac muscle fiber is bound by sarcolemma. It has a centrally placed nucleus. Myofibrils are
embedded in the sarcoplasm. Sarcomere of the cardiac muscle has all the contractile proteins,
namely actin, myosin, troponin and tropomyosin. Sarcotubular system in cardiac muscle is
similar to that of skeletal muscle.

Figure 6: Cardiac muscle cell with presence of gap junctions.

Electrical Potentials in Cardiac Muscle

Action potential in cardiac muscle is different from that of other tissues such as skeletal muscle,
smooth muscle and nervous tissue. Duration of the action potential in cardiac muscle is 250 to
350 msec (0.25 to 0.35 sec).
Phases of action potential
Action potential in a single cardiac muscle fiber occurs in four phases:
1. Initial depolarization
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2. Initial repolarization
3. A plateau or final depolarization
4. Final repolarization.

]\
FIGURE 7: Action potential in ventricular muscle.
1 = Depolarization, 2 = Initial rapid repolarization, 3 = Plateau, 4 = Final repolarization.

1. Initial Depolarization
Initial depolarization is very rapid and it lasts for about 2 msec (0.002 sec). Amplitude of
depolarization is about + 20 Mv
2. Initial Repolarization
Immediately after depolarization, there is an initial rapid repolarization for a short period of
about 2 msec. The end of rapid repolarization is represented by a notch.
3. Plateau or Final Depolarization
Afterwards, the muscle fiber remains in depolarized state for sometime before further
repolarization. It forms the plateau (stable period) in action potential curve. Due to long plateau
in action potential, the contraction time is also longer in cardiac muscle by 5 to 15 times than in
skeletal muscle.

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4. Final Repolarization
Final repolarization occurs after the plateau. It is a slow process and it lasts for about 50 to 80
msec before the re-establishment of resting membrane potential.

IONIC BASIS OF ACTION POTENTIAL IN CARDIAC MUSCLE

1. Initial Depolarization
Initial depolarization (first phase) is because of rapid opening of fast sodium channels and the
rapid influx of sodium ions, as in the case of skeletal muscle fiber.
2. Initial Repolarization
Initial repolarization is due to the transient (short duration) opening of potassium channels and
efflux of a small quantity of potassium ions from the muscle fiber. Simultaneously, the fast
sodium channels close.
3. Plateau or Final Depolarization
Plateau is due to the slow opening of calcium channels. These channels are kept open for a
longer period and cause influx of large number of calcium ions. Already the slow sodium
channels are opened, through which slow influx of sodium ions continues. Because of the entry
of calcium and sodium ions into the muscle fiber, positivity is maintained inside the muscle
fiber, producing prolonged depolarization, i.e. plateau. Calcium ions entering the muscle fiber
play an important role in the contractile process.
4. Final Repolarization
Final repolarization is due to efflux of potassium ions. Number of potassium ions moving out of
the muscle fiber exceeds the number of calcium ions moving in. It makes negativity inside,
resulting in final repolarization. Potassium efflux continues until the end of repolarization..
Restoration of Resting Membrane Potential
At the end of final repolarization, all sodium ions, which had entered the cell throughout the
process of action potential move out of the cell and potassium ions move into the cell, by
activation of sodium-potassium pump. Simultaneously, excess of calcium ions, which had
entered the muscle fiber also move out through sodium calcium pump. Thus, the resting
membrane potential is restored.

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Excitation-Contraction Coupling in Cardiac Muscle
The mechanism that couples excitation—an action potential in the plasma membrane of the
muscle cell— and contraction of heart muscle is an increase in the cell’s cytosolic calcium
concentration. As in skeletal muscle, the increase in cytosolic calcium concentration in cardiac
muscle is due mainly to the release of calcium from the sarcoplasmic reticulum. This calcium
combines with the regulator protein troponin, and cross-bridge formation between actin and
myosin is initiated.
But there is a difference between skeletal and cardiac muscle in the sequence of events by which
the action potential leads to increased release of calcium from the sarcoplasmic reticulum. In
both muscle types, the plasma membrane action potential spreads into the interior of muscle cells
via the T-tubules (the lumen of each tubule is continuous with the extracellular fluid). In skeletal
muscle the action potential in the T-tubules then opens calcium channels in the sarcoplasmic
reticulum by a physical coupling mechanism. In cardiac muscle (1) The action potential in the T-
tubule opens voltage-sensitive calcium channels in the T-tubule membrane itself; calcium
diffuses from the extracellular fluid through these channels into the cells, causing a small
increase in cytosolic calcium concentration in the region of the immediately adjacent
sarcoplasmic reticulum. (2) This small increase in calcium concentration then causes calcium
to bind to calcium receptors on the external surface of the sarcoplasmic reticulum membranes.
(3) These calcium sensitive receptors contain intrinsic calcium channels, and activation of the
receptors opens the channels, allowing a large net diffusion of calcium from the calcium-rich
interior of the sarcoplasmic reticulum into the cytosol (this is termed “calcium-induced calcium
release”). (4) It is mainly this calcium that causes the contraction. Thus, even though most of the
calcium causing contraction comes from the sarcoplasmic reticulum, the process—unlike that in
skeletal muscle—is dependent on the movement of extracellular calcium into the muscle, the
calcium then acting as the signal for release of the sarcoplasmic reticulum calcium.

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Refractory Period of the Heart
Refractory Period in Skeletal Muscle and Cardiac Muscle
In skeletal muscle, the refractory period is short. Absolute refractory period extends during
the first half of latent period, measuring about 0.005 sec. Relative refractory period extends
during the second half of latent period measuring 0.005 sec. So, the total refractory period is
0.01 sec.
Cardiac muscle has a long refractory period compared to skeletal muscle. Absolute refractory
period extends throughout the contraction period of cardiac muscle and its duration is 0.27
sec. Relative refractory period extends during first half of relaxation period, which is about
0.26 sec. So, the total refractory period is 0.53 sec.
Significance of Long Refractory Period in Cardiac Muscle
Long refractory period in cardiac muscle has three
advantages:
1. Summation of contractions does not occur
2. Fatigue does not occur
3. Tetanus does not occur.

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