University of Gondar

College of Medicine and Health Sciences

Department of Medical Physiology
Introduction to Physiology
For
Med II students
2019

1
 Objectives
At the end of this chapter the student will be able to:

1. Define physiology

2. Explain about body fluids

3. Explain homeostasis and regulatory mechanisms of the body

4. Discuss about cell physiology

5. Describe components of plasma membrane
6. Describe membrane physiology
7. Explain types of transport across plasma membrane
8. Cell to cell communication/signaling
9. Define membrane potential and its causes
10.Action potential 2
 Introduction to Physiology
• Humans have been interested in
– how their body works

• To treat disease and injury, we must first

understand the human body in its healthy state
– Physiology

3
 Introduction to Physiology…
 Physiology
 Knowledge of nature

 It is the study of the normal functioning of a living

organism and its component parts, including all its
chemical and physical processes
 It is the scientific study of normal mechanisms and
their interactions within a living system

4
 Introduction to Physiology…

 Fields of physiology
 Ranges from
 Simple micro organismal physiology to the most complex
human physiology

5
 Introduction to Physiology…
Human physiology
Explain the specific characteristics and mechanisms of the
human body that make it a living being.
We remain alive as a result of complex control systems
and specific characteristics like
Example
– Hunger makes us seek food, and
– fear makes us seek refuge.
– Sensations of cold make us look for warmth.
these special attributes allow us to exist under widely varying
conditions, which otherwise would make life impossible.
6
 Introduction to Physiology…
 An important part of physiology is understanding
 how different parts of the body are controlled,
 how they interact, and
 how they adapt to changing conditions

Physiology is a quantitative science

Physiological parameters are expressed in numbers

7
 Historical background of physiology
Aristotle (384-322 B.C.)
 Physiology- the functioning of all living organisms
Hippocrates (460-377 B.C.)

• Father of medicine

• physiology -the healing/health giving power of nature

• thereafter the field became closely associated with

medicine.

8
 Historical background of physiology…
 William Harvey in 1628
 Blood was pumped out of the heart through one set of vessels and

returned to the heart through another set.

 Do not know about micro circulation

 Claude Bernard, 19th C

 Described that every cell in body is bathed with the fluid env’t
called extracellular fluid(ECF).

 Develop the concept of a relatively stable internal environment

• He called this internal environment of the body as ECF(milieu

9
interior)
 Historical background of physiology…
Walter B cannon-
• He created the word homeostasis to describe the regulation of this
internal environment.

– Homeo - like/similar not same (homo)

– Stasis -a condition, not static/unchanging

• He defines homeostasis as

– a state of maintaining a similar/relatively constant condition in

the internal environment/ECF

10
Relationship b/n Physiology and other sciences
Physiology has a strong link with other disciplines

It is highly related to

Anatomy

Biochemistry

Pathology

Pharmacology etc

11
 Levels of the Organization of the Human Body
1. Chemical level

• Various atoms and molecules make up the body.

• Like all matter, human body is a combination of

specific atoms
• The most common atoms in the body are O2, N2, H2, C
• These common atoms and a few others combine to form the
molecules of life, such as proteins, carbohydrates, fats, and
nucleic acids
These important atoms and molecules are the inanimate
raw ingredients from which all living things arise
12
Levels of the Organization of the Human Body…

• The mere presence of collection of atoms & molecules does

not confer the unique characteristics of life

• These nonliving chemical components must be

arranged and packaged in very precise ways to
form a living entity.

13
 Levels of the Organization of the Human Body…
 Chemical level cell  tissue organ  system organism

14
 2. Cellular level
1. Cell

 The basic structural and functional unit of an organism

It is the smallest unit capable of carrying out the processes

associated with life

• Functional unit of life

 It is the smallest living unit of the human body

 But play a big role in making our body function properly

15
The entire body contains about 100 trillion cells
Each type of cell is specially adapted to perform one or
a few particular functions

Example-RBC-transport oxygen from lungs to the

tissues

Each cell has basic requirements to sustain it and

The body's organ systems are providing these many

cells with those basic needs (oxygen, food) and
16
remove waste products.
 There are many different types of cells in the body including:
Nerve cells
Blood cells
Epithelial cells and
Muscle cells

17
 2. Tissue
 When many identical cells are organized together it is called a tissue

 There are four types of tissues in the body:

1. Epithelial tissue

2. Connective tissue

3. Muscle tissue

4. Nervous tissue

3. Organ

 Organs are structures that are made of two or more different types of
tissues
18
4. System
 Consists of related organs that have a common function.
 There are 11 organ systems in the body
1. Respiratory System
2. Cardiovascular System
3. Digestive System
4. Urinary System
5. Reproductive System
6. Skeletal System
7. Muscular System
8. Integumentary System
9. Nervous System
10. Endocrine System
11. Lymphatic & Immune System
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 Renal Skeletal Muscular
CVS GIT RS System System system

5. Organism –it is the highest level of organization

e.g. Human
20
 Human Body fluid
• How much water is in the human body?

• In human physiology we often speak of standard values for

physiological functions,

– Based on the 70-kg young man/ average adult

• Approximate composition of an average adult human body is

– Water = 60% of body mass
– Proteins = 18% //
– Fats = 15% //
– Minerals = 7% //
 Body Fluid(BF= body water and its dissolved substances=60% Wgt

Example-Total body water(TBW) of a 70kg adult man ~42 L 21

 Human Body fluid…
 This 42 L is found distributed to in 2 compartments
1. Intracellular fluid compartment (ICF)

-Fluid inside the cell (28L) -2/3rd of TBW

2. Extracellular fluid compartment (ECF)

-fluid out side the cell(14 L) –1/3 of TBW.

-2 Subdivisions:

1. Blood plasma (1/4th of ECF) =3.5L

2. Interstitial fluid (3/4th of ECF )=10.5L

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23
24
Transcellular fluid
Special type of ECF

Accounts 1% to 3% of body weight

It includes
CSF

Aqueous & vitreous humor of the eye

Secretions of the digestive tract and associated organs

(saliva, bile, pancreatic juice)

Renal tubular fluid and bladder urine

synovial fluid and sweat 25

26
 Extracellular fluid compartment(ECF)

 1st described by Claude Bernard

 It is a fluid that surrounds all cells in the body

 It contains an optimum amount of important materials

needed by the cells to maintain life

 This ECF is in constant motion throughout the body

 So all cells live in essentially the same environment(ECF)

 Cells are capable of living & performing their special

functions as long as the proper concentrations of ECF
27
ICF ECF
 Water  Water
 High K+,Po43-,Mg2+, proteins  High Na+, Cl- , Ca2+
and HCO3
 Nutrients,
 Nutrients
 gases
 Gases: O2, CO2
 Hormones  Hormones
 Enzymes
Special mechanisms for transporting ions through the cell
membranes maintain the ion concentration differences between the
extracellular and intracellular fluids.

28
Normal values of ECF & ICF

29
 ECF & ICF differ strikingly in terms of their electrolyte
composition

 But the fluid compartments solute concentrations

(osmolarity) are normally equal (no an osmotic difference
be/n ICF and ECF)

 ECF
 Blood plasma,

 Interstitial fluid higher [protein] in plasma

Similar in others
 Lymph
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 Homeostasis
Homeostasis
 Homeo=similar

 stasis=condition

 Homeostasis is maintenance of nearly constant conditions in the

internal environment (ECF)

– But this does not mean that its composition are

absolutely unchanging

– Both external and internal factors continuously threaten

to disrupt homeostasis
31
 Homeostasis…

Example Example
Heat • Abnormalities in
Cold visceral organs
Lack of 02 • Abnormal
Pathogens & toxins growth of cells
• Autoimmune
diseases
• Inherited
disorders

32
 Homeostasis…
 Cells of multicellular animals do not tolerate much change in ECF
and depend on the constancy of ECF to maintain normal function.

 Therefore, when any factor starts to move the ECF away from
normal range of values

 the body systems initiate appropriate counter

reactions/compensatory mechanisms to minimize the change
For example
 when you drink a large volume of water-increased urine output and
protect your cells from dilution.

During exposure to a warm environment- Sweating

During exposure to a cold environment- shivering 33

 Homeostasis…
An organism is said to be in homeostasis when its
internal environment/ECF contains an optimum
amount of

Nutrients, gases

Electrolytes, water

Hormones, enzymes and others…

34
 Homeostasis…
 Essentially all organs of the body perform their functions to
maintain constant conditions in the ECF. For example

 Respiratory system(RS)

 The blood picks up oxygen in the alveoli, thus acquiring the

oxygen needed by the cells

 Carbon dioxide is released from the blood into the lung alveoli
for exhalation

So RS help to maintain the normal concentration of respiratory

gases in blood.

35
 Homeostasis…
Cardiovascular System(CVS)
 CVS-provides
Nutrients (glucose,aa,lipids),
Gases (O2)
Signaling molecules (hormones)
and
Removal of wastes (urea,
creatinine, CO2),

36
 Homeostasis…
 Gastrointestinal system

 Nutrients are absorbed into the ECF of the blood.

 Some waste products of metabolism are eliminated in the feces

 Renal system

 Removes unwanted substances from plasma

 Maintains constant ionic concentration

 Musculoskeletal System

 Provides motility for protection against adverse surroundings

 Allow movement to obtain the foods required for nutrition

 Hemopoiesis and mineral storage 37

 Homeostasis…
 Immune System

 protect the body from pathogens

 Integumentary System.

 provide a boundary b/n the body’s internal environment and the

outside world.

 cover, cushion, & protect the deeper tissues and organs of the body

 Temperature regulation and excretion of wastes

 Reproductive system
 Has less role for homeostasis
 Help maintain homeostasis by generating new beings to take the
place of those that are dying. 38
 Regulatory Systems of Homeostasis

The two controlling

bodies of homeostasis are Hormone
Nerve Impulse
1. Nervous system

2. Endocrine system
Receptor
NTs
Receptor
Effector cell

39
 Control pathways
• Any control system has three basic parts

1. Input signal

– consists of
• Regulated variable and

• Sensor

• Sensory pathway

– If the variable moves out of its desirable range, the sensor is

activated and sends a signal to the controller through sensory
pathway

40
 Control pathways
2. Controller
• Programmed to respond to certain input signals
• Receive and evaluates the incoming signal

• compares it with the set point/desired value, and

• Decides on an appropriate response and initiates the output

signal to bring the regulated variable back into the desired range.

• it is often a neuron or an endocrine cell.

3. Output signal

– carries out the appropriate response to bring the situation back to

within normal limits.
41
 Control pathways

Physiological control systems keep regulated variables within a desired

range during homeostasis. 42
 Control pathways
• Homeostasis may be maintained by local or long-distance pathways
1. Local Control
• Paracrine and autocrine signals are responsible
• a cell or tissue senses a change in its immediate vicinity & responds
– The response is restricted to the region where the change happens
Example
– When there is hypoxia, cells lining the small BVs sense the fall in
[O2] & respond by secreting a paracrine signal(CO2 & lactic acid)
• The paracrine molecule relaxes muscles in the BV wall, dilating
the blood vessel and bringing more blood and therefore more
oxygen to the area.
43
 Control pathways
2. Long-distance pathways/Reflex Control

• Coordination of the reaction lies outside the organ that carries out
the response

• Uses the nervous system, endocrine system, or both

to

– Receive input about a change,

– integrate the information, and react appropriately

44
Long-distance pathways/Reflex Control

Nervous system Endocrine system

Hormone
Nerve Impulse

Receptor
NTs
Receptor
Effector cell

45
 Homeostatic control systems
1. Feed-forward control
Used for responses made in anticipation of a change
Established before the change is developed

 Correction is by anticipation
Example
-  HR and RR before actual exercise
-  Digestive juice before food inter into GIT
- insulin while meal is still in the GIT(before digestion)
 Used to adapt & rapid rate of response to the change

46
 2. Feedback control
 Responses made after a change has been detected

 It alter the function of organs by increasing or decreasing

their activities

 There are two types of feedback mechanisms

1. Negative feedback mechanism/NFM

2. Positive feedback mechanism/PFM

47
 Negative Feedback Mechanism (NFM)
 It works by producing an effect which opposes the previous
condition (the initiating stimulus) of the organ
 Elements of negative feedback mechanism

48
 NFM…
Most homeostatic values of the body are controlled by
NFM

Example: control of

1. Blood Glucose Level

2. Body Temperature

3. Calcium

4. Arterial Blood Pressure etc

49
Control of Blood Glucose Level

50
Ca2+-homeostasis

51
Human thermoregulation

52
 Positive Feedback Mechanism (PFM)
It works by producing an effect which enhances or repeats
the same action like that of the starting stimulus.
The response of the system makes the deviation more
greater
PFMs are not homeostatic and are rare in healthy
individuals.
Positive feedback can sometimes be useful.
Examples
1. Blood clotting
2. Labor during child birth
3. Generation and propagation of the action potential
4. LH surge
53
1. Labor during child birth

54
 PFM..
2. Blood clotting is an example of a very valuable use of PFM.

• When a blood vessel is ruptured and a clot begins to form,

– multiple clotting factors are activated within the clot.

• Some of these enzymes act on other un-activated enzymes of the
immediately adjacent blood, thus causing more blood clotting.

• This process continues until the hole in the vessel is plugged and
bleeding no longer occurs

55
 PFM..
3. Generation and propagation of the action potential.
Stimulated nerve fiber

opening of Na+ channels

entry of few Na+

stimulates the opening of more and more Na+ channels

56
 PFM..
• Positive feedback can sometimes cause vicious cycles and
death
What would occur if blood pressure is controlled by
PFM?

57
 If the person is suddenly bleed 2L blood

decreased blood volume

decreased arterial pressure

diminishes coronary blood flow

weakening of the heart

further diminished pumping ability of the heart w/c leads to

further decrease in BP and coronary blood flow

the cycle repeats itself again and again until death occurs. 58
PFM…

59
Homeostatic values
1. Body fluid volume(TBW) = 42 L
ICF = 28L(2/3rd of TBW)
ECF = 14L(1/3rd of TBW)
Interstitial fluid = 11 L(3/4th of ECF)
 Plasma fluid = 3 L (1/4th of ECF)
2. Osmolality = 300 mosm/L, (285 – 300 mosm/L)
3. Body T. = 36.5 – 37.4OC
4. pH = 7.35 – 7.45
5. Blood Gases - PCO2 = 35 – 45 mm Hg
PO2 = 40 – 104 mm Hg
6. Electrolytes (ECF)
Ca2+ = 10 mg/dL or 5 meq/L
K+ = 4 meq/L
Na+ = 142 meq/L
Cl- = 103 meq/L
60
HCO3- = 27 meq/L
 Homeostatic values
7. Waste Products
Bilirubin = 0.5 mg/dl
Creatinine = 0.6 – 1.5 mg/dL
Blood urea nitrogen (BUN) = 8 – 25 mg/dL
Uric acid (s): Women = 2.3 – 6.6 mg/dL
Men = 3.6 – 8.5 mg/dL
8. Blood Glucose level (fasting): 70 – 110 mg/dL
9. Arterial Blood pressure (systemic circulation).
Systolic pressure = 120 mm Hg (90 – 140 mm Hg)
Diastolic pressure = 80 mm Hg (60 – 90 mm Hg)
Pulse pressure = 40 mm Hg
Mean BP = 96 mm Hg
Pulmonary AP = 25/10 mm Hg
Cardiac output = 5 L/min
Blood Flow = 5 L /min
10. RBC count = 4-6 millions/mm3
11. WBC count = 4000-11,000/mm3
12. Hb = 12-18 g/dl in F, 14-20 g/dl in M
13. Platelets = 150,000-450,000 61
 Disturbances of homeostasis
When there is lose in homeostasis, the organism tries to
compensate it.
– If compensation succeeds, wellness happens

– If compensation fails, illness or diseases happens

• Deviations from normal ranges = PATHOLOGY
• Disease: a state of disrupted homeostasis.
– Hypo/ Hyperthermia ….. ↓or↑ Temperature
– Hypo/ Hypercapnea ….. ↓or↑ PCO2
– Acidosis/Alkalosis ….. ↓or↑ PH
– Hypoxia/ Hyperoxia …. ↓or↑ PO2
– Hypo/ Hypercalcemia …. ↓or↑ Ca 2+
– Hypo/ Hyperglycemia … ↓or↑ Glucose
62
 Components of Cell
1. Plasma membrane

It is a sheet-like structure that surround (enclose) the cell,

It separates the cellular contents from the ECF

Regulates the passage of substances in and out

We will see later in membrane physiology section

64
 Nucleus
 It is the control center for the cells

 It contains the genes, which are units of heredity.

 Chemically each gene consists of highly compressed DNA in the

form of chromosomes

 Genes control cellular activity by determining the type of

 Proteins

 enzymes, and

other substances that are made by the cell

65
 Nucleus…
Nucleoli- site for Ribosomal RNA synthesis.

The nuclear contents are surrounded by a double walled

nuclear membrane.

The pores present in this membrane allow fluids,

electrolytes, RNA, and other materials to move between
the nuclear and cytoplasmic comportments.

66
 Nucleus…
Nucleus coordinates protein synthesis in ribosomes
Transcription phase of protein synthesis occur there
transcription translation
DNA RNA Protein synthesis

Following transcription, the mRNA leaves the

nucleus and travels to the cell's ribosomes, where
translation occurs

67
 Cellular organelles
• inner organs embedded within the cytoplasm of the cell.
These include

– Ribosomes

– Endoplasmic reticulum (ER)

– Golgi apparatus

– Mitochondria

– Lysosomes and

– Cytoskeletal system (microtubules & microfilaments).

68
Structure of human cell

69
 Cell organelles may be:
Non-membrane-limited Membrane-limited
 Nucleoli  Nucleus

 Ribosomes  Endoplasmic reticulum

 Microtubules  Golgi apparatus

 Microfilaments  Lysosomes

 Centrioles  Mitochondria

70
Ribosomes:
 Are the sites of protein synthesis in the cell
 Found in two forms:
1. Attached to the wall of ER or
2. As free ribosomes. They are found in two forms
I. Scattered in the cytoplasm and
II. Clustered (aggregated) to form functional units
called polyribosomes

71
Endoplasmic reticulum (ER)
It is an extensive membranous structure that
connects various parts of the inner cell.
ER is also connected with the nuclear membrane.
There are two types of ER:
1. Rough ER(rER)- site of protein synthesis
2. Smooth ER(sER)- is free of ribosome.
Function of sER
1. Synthesis of fatty acids, steroids, and lipids
2. Glycogen storage
3. Calcium storage
4. Drug metabolism (detoxification)

72
Golgi Complex
It acts as a receptacle/container for hormones and others
substances that the ER produces.

It then modifies and packages these substances ( proteins)

into secretary granules(vesicles).

73
 Mitochondria
• Mitochondria are the site of most ATP generation,

– Powerhouse of the cell

• Has outer and inner membrane, intermembrane space in

b/n which
– plays an important role in the production of ATP

• Inside the inner membrane, there is

– mitochondrial matrix

– matrix contains enzymes, ribosomes, granules, and DNA.

74
 Mitochondria…
• Mitochondria are unusual organelles in two ways.

1. They have their own unique DNA

2. Their ability to replicate themselves

– even when the cell to which they belong is not

undergoing cell division.

75
 Mitochondria…
• Major site of
ATP production

Oxygen utilization

Contains enzymes of krebs cycle and oxidative

phosphoryiation

76
 Lysosomes
Lysosomes are vesicular organelles that form by breaking
off from the Golgi apparatus and then dispersing
throughout the cytoplasm.

Contains aggregates of enzymes

Well developed in macrophages

Are called suicide bags

 They provide an intracellular digestive system that
allows the cell to digest
– damaged cellular structures
– harmful substances such as bacteria. 77
 Peroxisomes/small bodies
Are single membrane bounded organelles containing
enzymes; oxidases and catalases

Secrete chemical that converts harmful substances into

harmless

Example

Catalase is a type of oxidase produced by peroxisomes and

converts: H2O2 catalase H2O + O2

78
 Cytoskeleton
• The cytoskeleton is a flexible scaffolding of

– actin micro filaments,

– intermediate filaments

– microtubules

that extends throughout the cytoplasm.

79
 Functions of cytoskeletal
1. provides mechanical strength to the cell and
determining the shape of the cell

2. Stabilize the positions of organelles

3. Intracellular transport- The cytoskeleton helps

transport materials into the cell and within the
cytoplasm, serving as an intracellular railroad track for
moving organelles.

80
Membrane Physiology

81
 Plasma membrane/cell membrane
 It composed of proteins, lipids and carbohydrates in proportion of
1.Proteins (55 %)
2. Lipids (42 %)
 Phospholipids -25 %

Cholesterol -13 %

– make membranes impermeable to small water-soluble

molecules
– keeps membranes flexible over a wide range of
temperatures.
Neutral fats -4 %
3. Carbohydrate (3%)
82
 What determines the proportion of proteins in PM?

• The more metabolically active a membrane ,the more

proteins it contains.

• Composition of selected membranes

83
 Function of the plasma membrane
1. Separates cellular contents from the ECF

2. Regulates the passage of substances in and out.

It is semi-permeable allowing some subs to pass

through it excluding others. This creates unequal
distribution of ions on both sides of the membrane.

It allows oxygen and nutrients to enter the cell while

keeping toxins and waste products out

84
 Function of the plasma membrane…
3. It provides receptors for NTs, hormones and drugs
– Communication between the cell and its environment.
4. It is a means of cell to cell contact.

5. Structural support
– Proteins in the cell membrane hold the cytoskeleton
– Cell-cell and cell-matrix junctions stabilize the structure
of tissues.
5. For generation & transmission of electrical impulse in
nerves & muscle.
85
 Components of cell membrane
1. Lipid
 Lipids form the basic structure of the membrane.

 The lipid molecules are arranged in two parallel rows,

forming a lipid bilayer.

86
 Phospholipids
• Polar Phosphate head
– Hydrophilic(soluble in water) Phosphate
• Fatty acid tails “attracted to water”
– Hydrophobic(that does not mix
with water ) Fatty acid
• Arranged as a bilayer
“repelled by water”

87
Fluid mosaic model of a plasma membrane
 Phospholipids…
 The physical orientation of the lipid
bilayer structures is that the

hydrophilic ends of the lipid

bilayer molecules line up facing
the ICF and ECF.

The hydrophobic tails of the

molecules face each other in the
interior of the bilayer.
88
 Arranged as a Phospholipid bilayer
• Serves as a cellular barrier / border
ECF
sugar H2O salt
polar
hydrophilic
heads

nonpolar
hydrophobic impermeable to polar molecules
tails

polar
hydrophilic
heads
waste lipids
89
ICF
 Permeability to polar molecules?
 Membrane becomes semi-permeable via protein
channels
– Specific channels allow specific material across cell
membrane

ECF

inside cell H2O aa sugar

salt 90
NH3
ICF
 Fat soluble substances such as

– O2, CO2, and lipids can easily penetrate PM

 The lipid bilayer portion of the cell membrane is impermeable

 Ions, polar molecules( water and water soluble substances) such as

ions, glucose, urea and others

 very large molecules (such as proteins),

So such substances enter cells with more difficulty or may not enter at
all.

91
 2. Membrane Proteins
• Membrane Proteins Function as

1. Structural proteins

• to connect the membrane to the cytoskeleton

– to maintain the shape of the cell

• to create cell junctions that hold tissues together

– such as tight junctions and gap junctions

• to attach cells to the extracellular matrix

92
2. Membrane Proteins…
2. Enzymes

3. Receptors

4. Transporters
• Channels

• Carriers

93
94
 Types of membrane proteins
A. Intrinsic/Integral proteins
 Exist as globular units running through the width of the cell
membrane;

 Partly hydrophilic (polar and protruding to cell surface) and

partly hydrophobic (non-polar and embedded in the lipid bilayer).
 Protruding part may often carry CHO chains or lipids attached to
their tips like flags.
 Tightly associated with membrane and
 Account for about 70% of the membrane proteins.

95
Intrinsic/Integral proteins…

 Many of them provide structural channels through w/c

polar substances can diffuse in and out of the cell.

Trans membrane proteins serve as:

 Channels through which ions, water and other
molecules pass. Their name is also given accordingly

 Carriers which actively transports material across the

bilayer e.g. glucose
96
 Carrier proteins
• They bind with specific substrates and carry them across
PM by changing conformation.

– Small organic molecules (such as glucose and amino

acids) that are too large to pass through channels cross
membranes using carriers.

– Ions such as Na+ and K+ may move by carriers as well

as through channels.

97
 1. The molecule binds to
the carrier on one side
of the membrane

2. This binding changes

conformation of the
carrier so that the
opening closes

3. the opposite side of the

carrier opens to the other
side of the membrane,
carrier then releases 98
 Ion channels
Are integral proteins that span the membrane and, when
open, permit the passage of certain ions.
May be
Open (leak channels)
Closed (gated channels)
When the channel is open, the ion(s) for which it is
selective can flow through.
When the channel is closed, ions cannot flow through.
Opening and closing of channels are controlled by gates
There are 4 kinds of gated channels

99
 What controls the opening and closing of gated channels?

1. Voltage-gated channels
-Are opened or closed by changes in membrane potential.
2. Chemically gated channels
-Are opened or closed by hormones, or NTs.
3. Mechanically gated channels-
• respond to stretching or other mechanical deformation
e.g-Many channels associated with the sense of
touch(somatosensation)

4. Thermally gated channels-

100
 respond to local changes in temperature (heat or cold).
B. Peripheral or extrinsic proteins:
 Hydrophilic and readily dissociated from membrane.

 Free, floating on the surface (inside and outside of the membrane

 Account for about 30% of the membrane proteins.

 Bind specific hormones and proteins on cell membrane.

 Peripheral proteins that bind to the intracellular surface contribute
to the cytoskeleton.

101
102
3. Carbohydrates(Membrane carbohydrates)
 Found exclusively on external surface of cell attached with protruded

1. Proteins (glyco-proteins)

• Glycoproteins on the cell surface play a key role in the body s

immune response-ABO blood grouping

2. Lipid (glyco-lipid )

Function

• Cell recognition

• Site of receptors for NTs, hormones and drugs.

• Cell to cell attachment- Structural stability

103
104
 Transport through cell membrane
What needs to cross the PM?
Nutrients and wastes
Signaling molecules
Fluid
Certain ions
The PM is a very important structure which functions
to allow certain substances to enter or leave the cell
still excluding others to cross the membrane

105
 Transport through cell membrane…
Such a membrane is referred to as "selective permeable“
("semipermeable")

Both protein & phospholipids portion of the membrane

are involved in the membrane permeability.

106
 Transport through cell membrane…
I. Transport of ions and small solute molecules across the plasma membrane.
1. Passive transport
 Do not require energy (ATP) from the cell
– Uses only the energy of molecular movement of substances/Uses the
kinetic energy inherent in molecules. It includes
 Simple diffusion
 Facilitated diffusion
 Osmosis
2. Active transport
 Require energy (ATP) from the cell's reserves to "power" transport of
substances. It includes
 Primary active transport
 Secondary active transport
107
 Transport through the cell membrane…
II. Transports large particles via a vesicle-like sac across
PM takes place by vesicular transport

1. Endocytosis

2. Exocytosis

108
 1.Simple Diffusion
 Diffusion is passive movement of uncharged substances down
their concentration gradient.

 Factors affecting the net rate of diffusion

 Lipid solubility of the subs

 Concentration difference or Pressure difference

 Membrane permeability- this is again affected by

Membrane Thickness
No of ion channels per unit area
Temperature: T =  thermal motion of molecule
permeability
MW (molecular weight) 109
 Simple Diffusion…
 Rate of diffusion is determined by the following factors
summarized in the formula shown below.
C.A. T.S
Rate of diffusion = D MW

Where, C = Change of concentration

S = Solubility in lipid of the sub.
A = Surface area of the membrane
T = Temperature
D = Distance or membrane thickness
MW = Molecular Wgt of substances
• Examples: Substances that are transported by simple diffusion are
CO2, O2, alcohol, lipid soluble drugs and ions through specific
channels.

110
 2. Facilitated diffusion
 Do not need energy
Glucose
 Transports substances down their
concentration gradient
ECF
 Is more rapid than simple diffusion.
Cell membrane
 Is carrier-mediated and therefore
ICF
exhibits specificity and saturation

 Examples: transport of glucose,

Carrier protein
proteins. (Macromolecules)

111
 Facilitated diffusion…
 Unlike simple diffusion the
rate of facilitated diffusion
increases as the
concentration gradient
increases until all of the
carrier sites are filled.
 At this point, the rate of
diffusion can no longer
increase with increasing
particle concentration.
 This is called saturation, Fig. Effect of concentration of a substance on
rate of diffusion by simple diffusion and
facilitated diffusion.
112
 3. Osmosis
 It is movement of H2O from an area of
higher amount of water to an area of
lower amount of water through the semi
permeable membrane.

 The direction of movement of water is

governed by the amount of osmoticaly
active particles (solutes).
 The pressure that opposes osmosis of
water is called osmotic pressure
 H2O molecules can not traverse the lipid
bilayer simply. Instead they pass through
specific water channels called aquaporins: 113
2 requirements for osmosis:

1. Difference in [solute] on the 2 sides of PM

2. Membrane must be impermeable to the solute

• Osmotically active solutes:

– Solutes that cannot pass freely through the

membrane

114
 Tonicity
• It is the ability of a solution to change the shape of a cell
immersed in it due to changes in the cell’s water volume.

A solution with the same concentration of non-penetrating

solutes( as those found in cells) are isotonic, i.e., “the

same tonicity
Cells exposed to such solution retain their normal shape
and exhibit no net gain or loss of water.

Most IV solutions are isotonic (e.g. 0.9% saline or 5%

115
glucose).
 Tonicity
Solution Types:
1. Isotonic solution
 A solution that has the same amount of solute as the solution
it is compared to.

2. Hypotonic solution
 A solution that has a lesser concentration of solute than the
solution it is compared to.

3. Hypertonic solution
 A solution that has a greater concentration of solute than the
solution it is compared to. 116
 Active transport
Substances are transported against concentration
gradient, up hill direction.

Consumes energy in the form of ATP

 Carrier protein is involved

Used for the transport of Na+, K+, Ca2+, Fe2+, H+, Cl-

1. Primary/direct active transport

2. Secondary active transport

117
 Active transport…
Common examples of primary active transport

118
 Active transport…
• Many primary active transporters are known as ATPases
– Because primary active transport uses ATP as its energy source,.

• ase =an enzyme, and

• ATP= the substrate upon which the enzyme is acting

• These enzymes hydrolyze ATP to ADP and inorganic

phosphate (Pi), releasing usable energy in the process

119
Examples of primary active transport
1. Na-K-Pump/Na+ - K+ ATPase
 It is a carrier protein that is made up of two
subunits.
 It has 3 binding sites for Na+ inside and
 2 binding sites for K+ on the outside
 It pumps 3Na+ outward and 2K+ inward
 It maintains electropositive outside and
electro negativity inside.
 Both Na and k are transported against their
electrochemical gradients.
 It has ATPase activity inside.
ATP = ADP + ---P + energy.
 Energy brings conformational change of
the pump so that Na+ pumped outward and
K+ inward.
 Creates an electrical potential across the cell
membrane
120
Examples of primary active transport…

121
Mechanism of the Na*-K*-ATPase
 Examples of primary active transport…
2. Calcium pumps/Ca2+-ATPases

– Found in the membrane of the

• Endoplasmic reticulum, and,

• Sarcoplasmic reticulum (in muscle cells)

– They pump calcium ions from the cytosol of the cell
either into the extracellular space or into the lumen of
these organelles.
– The organelles store calcium and, as a result, help
maintain a low cytosolic concentration of this ion
122
 Examples of primary active transport…
3. H+/K+-ATPase

– It is present in the luminal membrane of the parietal cells (acid-

secreting) glands of the stomach.

– pumping protons into the lumen of the stomach in exchange for

potassium ions,

– So it maintains the low pH in the stomach that is necessary for

proper digestion.

– It is also found in the colon and collecting ducts of the kidney.

– Its role in the kidney is to secrete H+ ions into the urine, when
blood pH falls, and to reabsorb K+ ions 123
 Examples of primary active transport…
4. H+-ATPases/Proton pumps

– Found in the membranes of the lysosomes & Golgi apparatus.

– They pump protons from cytosol into these organelles, keeping

the inside of the organelles more acidic than the rest of the cell.

– They are also found in PM of bone and kidney cells.

– The secretion of protons by the bone cells (osteoclasts) helps to
solubilize the bone mineral and creates an acidic environment for
bone breakdown by enzymes.
– The proton pump in the kidney is present in the same cells
(intercalated) as the H+/K+-ATPase and helps to secrete H+ ions
into the urine when blood pH falls.

124
2. Secondary/indirect active
transport
Carrier protein is
involved
Consumes energy

 The movement of a molecule down its concentration

gradient( usually Na+) provides energy for the "uphill"
transport of the other solute(s). i.e. metabolic energy is not
directly used but indirectly from the Na gradient .

125
Mechanism of the SGLT transporter.
126
 Active transport…
• So secondary active transport uses potential energy stored
in the concentration gradient of one molecule to push
other molecules against their concentration gradient.

• All secondary active transport ultimately depends on

– primary active transport because the concentration gradients that
drive secondary transport are created using energy from ATP.

127
• The mechanism for both types of active transport appears
to be similar to that for facilitated diffusion.

– A substrate binds to a membrane carrier

– carrier changes conformation,

– Releasing the substrate into opposite compartment.

• Active transport differs from facilitated diffusion b/c

conformation change in the carrier protein requires
energy input.
128
Transport through the cell membrane…

ECF

ICF

129
Transport through the cell…
membrane…

130
 Vesicular transport
• What happens to the many macromolecules that are too
large to enter or leave cells through protein channels or
carriers?

• For transport of macromolecules and particles:

1. Endocytosis
• Pinocytosis- cell drinking
• Phagocytosis: cell eating
• Receptor-mediated endocytosis
2. Exocytosis
131
 Vesicular transport…
1. Endocytosis:-
 cells internalize extracelluar material
 Engulfing of materials by invaginating the outer part of a
cell membrane until it buds off within the cytoplasm
a. Phagocytosis: cell eating
 Is the process by which bacteria, dead tissue, or other material
are engulfed by cells.
 substance is a solid
 Phagocytic cell(macrophages)
are almost equal size to engulfed sub.

132
b. Pinocytosis- cell drinking :
 Is a similar process like phagocytosis but
the substances ingested are in solution.
the vesicles are much smaller in size
Invagination occurs into cell and pinches off to form
boundary of an intracellular vesicle, vacuole or
tubule.

133
2. Exocytosis - “Cell vomiting”
E.g. Releases of NTs, digestive
enzymes and some hormones.

N.B- Vesicular transport also uses energy 134

 Junctions between Cells
Multicellular organisms requires specific interaction b/n
cells
– to hold the cells together
– to communicate in order to coordinate activities
This is done through junctions

Types of junctions

– Tight junctions/occluding junctions

– Gap junctions/communicating junctions

– Anchoring junctions
135
 1. Tight junctions
Helps PM of adjacent cells to fuse together
Forming an impermeable junction

Designed to restrict movement of material b/n the cells

They link through the help of proteins called claudins

and occludins,
Example-
– Tight junctions in the GIT and kidney prevent most substances
from moving b/n external & internal environments

– They also create the BBB that prevents entry of harmful

substances from blood ECF of the brain
Tight junctions…

137
 2. Gap Junctions
• They are the simplest cell-cell junctions

• The adjacent PMs are very close, and the cells are connected by
hollow cylinders called connexons

– chemical & electrical signals pass rapidly from one cell to the next

• The channels are able to open and close, regulating the movement of
small molecules and ions through them.

• They are found in muscle and nerve cells,

• They are also important in cell-to-cell communication in many tissues,

including the liver, pancreas, ovary, and thyroid gland.

138
Gap Junctions…

139
 3. Anchoring junctions
• They are like buttons or zippers that tie cells together and
hold them in position within a tissue.

• They attach

1. Cells to each other using proteins called cadherins

• Cell-cell anchoring junctions

2. Cell to extracellular matrix using proteins called

integrin's

• Cell matrix anchoring junctions.

140
 Anchoring junctions…
• The protein linkage of these junctions is very strong

– allowing sheets of tissue in skin and lining body

cavities to resist damage from stretching and twisting.

141
 Anchoring junctions…
Desmosomes
– localized patches that hold two cells tightly together
– They are the strongest cell-cell junctions

– They may be small points of contact b/n two cells (spot

desmosomes) or bands that encircle the entire cell (belt
desmosomes)

– Mostly found in tissues that are subject to constant mechanical

stress such as skin and heart

142
143
Membrane Potential

144
 Excitable Tissues

Are tissues which are capable

of producing impulse/action
potential on proper stimulation

Two types of excitable tissues

1. Nerve tissue &

2. Muscle tissue

145
 Neurons

 Neurons are functional & structural units

of the nervous system.
 Specialized to conduct information from one
part of the body to another
 A neuron has 3 distinct parts. These are:
Cell body , Dendrites and Axon
1. Dendrites
Receive incoming signals
Convey info towards the soma through
the use of graded potentials 146
 2.Soma( cell body)

Contains rER(Nissl body)

– responsible for synthesis of
NTs
Acts as a receptive service

147
 Neuron…
• 3. Axons:
• Originates from axon hillock
• Transmit APs from soma toward the end of the axon where it cause NT
release
 The tips of most axon terminals swell into synaptic end bulbs.
 These bulb-shaped structures contain synaptic vesicles
 The NT molecules released from synaptic vesicles are the means of
communication at a synapse.

148
 Membrane potential
 All cells have a voltage difference across their plasma membrane.
• This is called membrane potential.

 It is a distribution of charge across the cell membrane, measured in

millivolts (mV).
 The standard is to compare the inside of the cell relative to the outside,
so the membrane potential is a value representing the charge on the
intracellular side of the membrane based on the outside being zero
 Changes in membrane potential are due to changes in ion movement across the
membrane.
 The membrane potential (VM) at rest is called resting membrane potential
(RMP).
 At rest, there are electropositivity out and electronegativity inside in PM of the
neuron.
149
 Membrane potential

An average value for the

RMP of neurons is -70 mV
That is, the potential
inside the fiber is 70mv
more negative than the
potential in the ECF on
Figure . Measuring Charge across a Membrane with a the outside of the fiber.
Voltmeter
 What are the causes of the RMP?
1. An outward diffusion of K+ through K+ leak channels.

2. The Na+/K+ pump is constantly pumping 3 Na+ ions out and 2 K+

ions in for every ATP used.

3. There are protein anions (i.e., negatively charged proteins) within

the ICF that cannot travel through the PM.

151
 Basic terms

Stimulus :
Any change in the environment (internal or external
environmental condition of the cell).

Excitability:
The ability to respond to a stimulus and convert it
into an action potential

Threshold stimulus:
Any stimulus strong enough to initiate nerve impulse 152
 Basic terms…

Depolarization:
Membrane potential becomes less negative than RMP
(-70 mV)

Repolarization:
When the membrane returns to RMP following
depolarization

Hyperpolarization:
Membrane potential become more negative than RMP
153
• There are two basic forms of electrical signals:

1. Graded potentials

• Local membrane potential change in small, specialized region of

excitable cell membranes

 E.g- RMP changes from -70 mv to -60 mv (a 10mv change).

 They are depolarization's or hyperpolarization's that occur in the

dendrites and cell body

 It is due to Na+ entry at the small specialized region of plasma

membrane

154
Current Flow During a Graded Potential
 Graded Potential

Graded Potential spread by passive Current flow

 Graded potential…
 Magnitude of graded potential varies directly with the magnitude of
the triggering event

– The stronger a triggering event, the larger the resultant graded

Potential

• May ultimately causes an AP.

– The weaker triggering event/stimulus

• the graded potential dies out without triggering an AP

 Graded potentials die over short distances

• Example of Graded Potential:

- Receptor Potential, Pace-maker Potential, end plate potential

 2. Action Potential
• AP is an immediate change of the RMP into depolarization that is
followed by reestablishment of the RMP (repolarization).
 If RMP changes from -70 mv to threshold level (-50 mV),
→voltage
gated Na+ channels open and → Na+ influx → depolarization. Na+
channels become inactivated soon. Then opening of voltage gated
K+ channels →K+ efflux → repolarization.

158
 Action potential…
• Axon membrane has high density
of voltage gated sodium channels.
• This molecular distinction enables
axon to generate and conduct APs.
• The region of membrane where
APs are normally generated is
called the spike initiation zone.
The arrow indicates direction of
AP propagation.
 Action potential
Action potential/ Spike/ Firing potential
Action potential is a Rapid , conductive , and
Reversible change of the membrane
potential(Vm) after the cell is stimulated.
Brief & large changes in Vm that
conveys information within the
nervous system & muscles
 AP travels along the PM undiminished

– B/c it develops at one point in the PM,

and regenerates an identical AP at the
next point in the membrane

160
Action Potentials
Voltage-Gated Sodium Channels

Voltage-Gated Potassium Channel

Action Potentials
 Action potential…
AP occurs only if the change in membrane potential at the axon hillock
reaches threshold level and above.

Action Potential follows All or None Law.

AP has 3 phases

1. Resting phase

2. Depolarization/rising phase

3. Repolarization/falling phase

164
 Phases of AP
• Resting Stage.

– It is the RMP before the action potential begins

– The membrane is said to be “polarized” during this

stage because of the −90 millivolts negative membrane
potential that is present.

– All voltage-gated channels closed

165
 Phases of AP…

• Depolarization Stage/Rising
Rising phase/ depolarization
phase
– When the change in Vm reaches
threshold level voltage-gated Na
Falling
channels open (Na+ activation gate phase/repolarizatio
n
opens) and

– Na influx will occur & causes

depolarization

166
 Phases of AP…
• Repolarization Stage/falling phase
– When it reaches +35, Na+ inactivation gate closes/inactivated
– Voltage-gated K channels open up, K efflux occurs-
Repolarization occurs
– On return to resting potential, Na+ activation gate closes and
inactivation gate opens, resetting channel to respond to another
depolarizing triggering event
– Further outward movement of K+ through still-open K+ channel
briefly hyperpolarizes membrane, which generates after
hyperpolarization.
K+ channels are slow to open and slow to close. This causes
hyperpolarization
• K+ activation gate closes, and membrane returns to resting
potential. 167
• The Na+/K+ pump gradually restores the concentration
gradients disrupted by action potentials.

– Sodium is pumped into the ECF

– Potassium is pumped into the ICF

168
Phases of action
potential:
1. Resting phase
2. Depolarization
3. Repolarization

169
 Voltage-Gated Na+ Channels

2 gates
1
1. Activation gates
 Voltage-dependent
 Opens with depolarization
 Fast opening
––

170
 Voltage-Gated Na+ Channels

2. Inactivation gates
 Voltage-dependent
 Closes with depolarization
 Slow opening

171
 Voltage-Gated K+ Channels

• One gate
• Voltage-dependent (sensitive
to depolarization)
• Time-dependent
– Opens more slowly than Na
channels
• Slow closing results in
hyperpolarization
172
 Refractory Periods

 It is the period during which no new action potential can be initiated

 Two types refractory period

1. Absolute refractory period( ARP)

 The period during which a 2nd AP cannot be elicited(even with a

supra threshold stimulus) in an excitable fiber as long as the
membrane is still depolarized from the preceding AP

 A Na+ channel cannot be involved in another AP until the

inactivation gate has been reset.

173
 ARP…
 The reason for this restriction is
that after the AP is initiated, the
sodium channels become
inactivated and even extra +35

threshold stimulus will not open

the inactivation gates. -90

– Because of the closure of

inactivation gate outside
inside

174
 2. Relative refractory period
 Follows ARP
 During hyperpolarization phase, Na+
channels begin to recover from
inactivation.
 As a result, even though, there is still +35

K loss in this phase second action

potential can be produced by very
strong stimulus. -90

outside
inside

175
Refractory period

176
 Action potential is an ALL OR NONE EVENT (It happens
completely or it does not occur at all).

 The AP fails to occur if the stimulus is sub threshold in

magnitude (it does not occur at all), OR

 It occurs with constant amplitude regardless of the strength of the

stimulus if the stimulus is at or above threshold intensity(It
happens completely, no small or large AP).

 Once threshold intensity is reached, a full-fledged action potential

is produced .Further increases in the intensity of a stimulus
produce no increment or other change in the AP (b/c all Na+
channels open at threshold stimuli) 177
 Conduction of Action Potential

 Opening of mechanically or chemically or voltage gated Na channels

create local potential on the membrane
 local potential may reach to threshold potential
 At threshold potential, voltage gated Na channels will open, AP
formed
 During entry of Na, some sodium ions will diffuse to the adjacent
membrane and cause membrane potential change(create another
threshold potential)
 Another action potential is generated
 This event continuous like this for the rest of the membrane down to
the synaptic knob.
 In each interval Na-K pump restore RMP
 So the AP is generated at the axon hillock, will travel all the way
 Aps are conducted, or propagated, throughout the entire membrane 178

in none decremental fashion

 Factors affecting rate of AP conduction through axon

1. Presence or absence of myelination

 Myelinated axons has faster rate of AP conduction than

unmyelinated axons
Nodes of Ranvier
• Region of concentrated voltage-
gated Na and K channels.
Factors affecting rate of AP conduction …
 Factors affecting rate of AP conduction …

 The manner in which it travels depends on whether the neuron is

myelinated or unmyelinated.

– Unmyelinated neurons

• Sweeping /continuous conduction of an AP

– Myelinated neurons

• jumping /saltatory conduction of an AP

• Myelin sheath act as electrical insulation

 Continuous (Sweeping) Conduction

 Occurs in unmyelinated
axons.

 The whole length of the

membrane is depolarized (AP
occurs on whole length of the
axon membrane)
 Velocity of conduction is slow
 Consumes large amount of
energy

182
Saltatory (Jumping) Conduction

 Occurs in myelinated axons.

 AP occurs at the axon of nodes of
Ranvier.
 Velocity of conduction is faster
(50 times faster than the fastest
unmyelinated fibers).
 Consumes few amount of energy
(Economizes ATP)
183
 Saltatory Conduction

 Nodes of Ranvier
• Region of concentrated voltage-gated Na channels.

184
 Factors affecting rate of AP conduction …

2. Diameter of fiber (size of nerve fiber)

• An axon with a large diameter conduct an AP faster
than axon with a small diameter .
3. Age
• Slower in babies and elderly
4. Temperature
• When warmed, nerve fibers conduct impulse at
highest speed; when cooled at lower speed.
185
 Synapses
• The junction between two cells in which one must be a neuron.
• The region where there is a transfer of message from a neuron to
the next.
There are 3 types of synapses

1. Neuroneuronal junction

-the junction b/n two neuron (Presynaptic and postsynaptic neuron)

2. Neuromuscular junction

- the junction between neuron & muscle.

3. Neuroglandualr junction

-the junction b/n neuron & gland 186

 Synapses …

• There are 3 types of neuroneuronal junctions

1. Axo-dendritic junctions
2. Axo-somatic junctions
3. Axo-axonic junctions

187
 Synaptic Transmission

 Two types of synapses:

– Electrical synapses and

– Chemical synapses

1. Electrical synapses

 Allow current to flow from one excitable cell to the next via gap
junctions(b/n the pre- and postsynaptic neurons)

 These gap junctions allow the transmission of the depolarization

wave directly from the pre- to the postsynaptic membrane

 Gap junctions are more numerous in smooth muscle and cardiac

188
muscle.
 Electrical synapses…

 Characteristics

 Are extremely rapid,

 Relatively rare and

 Have very little physiological

significance .

 An AP in one neuron always leads to

an AP in the connected neuron

189
 2. Chemical Synapses
 More common than electrical synapse
 One neuron will transmit impulse to
 another neuron or
 muscle or by releasing chemicals(NTs)
 gland cell
 Acts slower than electrical synapses
 b/c the NT must diffuse across the synaptic cleft to
bind the receptor.

190
 Components of AxoSomatic synapse

1. Presynaptic terminal
contains neurotransmitter (NT)
2. Synaptic cleft
contains ECF and Enzymes
3. Postsynaptic neuron
contains receptor for the action of
NT

191
 Mechanism of Chemical Synaptic Transmission

• An AP reaches the presynaptic axon terminal of the presynaptic

cell and causes V-gated Ca2+ channels to open.

• Ca2+ rushes in, binds to regulatory proteins & initiates NT release

by exocytosis.

• NTs diffuse across the synaptic cleft and then bind to specific
receptors on the postsynaptic membrane and initiate postsynaptic
potentials.

• NT-Receptor interaction results in either EPSP or IPSP.

192
Mechanism of Chemical Synaptic Transmission…cont’d
• When the NT-R combination triggers
the opening of ligand gated Na-
channels, this leads to membrane
depolarization, EPSP.
e.g. Ach on Nicotinic receptor
• When the NT-R combination triggers
the opening of ligand gated K or Cl-
channels, this leads to membrane
hyperpolarization, IPSP.
e.g. GABA on GABAb receptor
193
 Excitatory Vs Inhibitory Synapses
• Excitatory
- Occurs when there is opening of Na channel

- depolarization

- more likely to have action potential of postsynaptic cell

• Inhibitory
• hyperpolarizes the cell (less likely to have action potential)

• Occurs when there is opening of K and Cl channels

– K moves out
Produce IPSP
– Cl moves in
194
Excitatory Synapses Inhibitory Synapses

195
 Properties of chemical synaptic transmission

Unidirectional conduction
Synaptic delay (0.5 -1.0m/s)
o The time required for the multiple steps in chemical
neurotransmission to occur.
Fatigue
- Decrease in response of postsynaptic neurons after
repetitive stimulation by the presynaptic neurons possibly
resulting from Depletion of NT stores from the
presynaptic terminal. 196
Factors Affecting Synaptic transmission
PH

- Alkalosis ↑ Synaptic transmission

- Acidosis ↓ Synaptic transmission

Hypoxia ↓ Synaptic transmission

Drugs

- Caffeine, Theophylline, Theobromine, Strychnine

↑Synaptic transmission

- Hypnotics, Anesthetics, tranquilizers

↓ Synaptic transmission
197
 Summary of Action potential vs Graded potential
Action Potential Graded potential
1. Propagated 1. Non propagated

2. Amplitude varies with condition of the

2. Amplitude is independent of the
initiating event
initiating event.
3. Graded response(small, large… and these
3. No large/small AP and it can not be graded responses can be summated
summated/it is stereotypical 4. Has no refractory period

3. Has refractory period 5. Is conducted decrementally, amplitude

decreases with distance
4. Not affected by distance
6. Can be depolarization or repolarization
5. Is depolarization with an overshoot
7. Initiated by NTs, drugs, hormones or
6. Initiated by membrane
spontaneously.
depolarization.
8. Does not obey all or none law.198
7. Obeys all or none law.
 Cell to Cell communication…
Cell to cell
communication is very
important for multicellular
organisms.

 communication by

1. autocrine

2. paracrine

3. endocrine &

4. neurocrine controls
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 Cell to Cell communication…
1. Endocrine signals

 Through hormones produced by endocrine cells

 Hormones travel through the blood to reach to their target cells

2. Paracrine signals

 Target only cells in the surrounding area of the releasing cell.

Example =histamine, a chemical released from damaged cells.

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 3. Autocrine signaling
• Affect only cells that are of the same cell type as the emitting cell.

• Paracrine and autocrine signal molecules reach their target cells by

diffusing through the interstitial fluid

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 Cellular transduction process
• Cellular transduction process-
– will be covered by your biochemistry course

1. cAMP cascade & phosphorylation

2. Inositol-triphosphate

3. Diacyl glycerol

4. Calcium as a second messenger

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THANK YOU!!

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