Physiology of the Nerve

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 Excitable Tissues
• In the body there are two type of excitable tissues: Nerve &
Muscle.
• The term excitability refers to an ability of a tissue to receive
stimuli & respond to them.
• These stimuli can be electrical, chemical, mechanical or
thermal.
• Excitable tissues respond to various stimuli by rapidly
changing their resting membrane potentials (RMP) &
generating electrochemical impulses (action potentials, AP).
• Nerve & muscle cell are capable of producing electrical
signals when exited. Once started, APs is propagated
throughout an excitable cell.
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 Physiology of the Nerve
• A network of billions of nerve cells (neurons) linked
together in a highly organized fashion to form the rapid
control center of the body.
• Functions of the NS include:
– Integrating center for homeostasis, and almost for all
other body functions like: for our perceptions, behaviors,
& memories, and initiates all voluntary movements.
– The branch of medical science that deals with the normal
functioning & disorders of the NS is neurology.
– A neurologist is a physician who specializes in the Dx &
Rx of disorders of the NS.
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 Nervous system vs. Endocrine System
 Similarities:
– Both monitor stimuli & react so as to maintain
homeostasis.
 Differences:
– The nervous system is a rapid, fast-acting system
– The endocrine system acts slower (via blood-borne
chemical signals called hormones & its actions are
usually much longer lasting.

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 Nerve tissue
There are two principal cell types that make the NS; called
neurons & neuroglial cells.
Neurons Neuroglial cells
• Neurons are functional units of the NS • Supporting cells
(functional, signal conducting cells) • Generally they are
• Neurons are specialized for smaller but 20 times
– generation & transmission of nerve outnumber than
impulses, neurons
– sensory function,
• Can multiply after
– generation of thought,
maturation
– storage of memory,
• Potential causes of
– integrates idea, and
– coordinates muscular activities
gliomas (brain
tumour) 5
 Neuroglia
The neuroglia are non excitable
cells found in association with
neurons.
They provide supporting &
protecting functions to the
activities of neurons.
Six types of supporting cells are:
1. Microglia
2. Astrocytes
3. Oligodendrocytes
4. Ependymal cells
5. Schwann cells
6. Satellite cells 6
7
 Types of Neurglia in the CNS
There are four types of neurglial cells in the CNS:
Microglia:- specialized macrophages capable of
phgocytosis & protecting the CNS.
Astrocytes: - provide nourishment to the CNS
- interconnects axons with blood vessels
- make up the BBB (blood brain barrier)
Oligodendrocytes:- Produces myelin sheath w/c provides
electrical insulation for axons of neurons in the CNS.
Ependymal cells:- line the cavity of the CNS & make up
the walls of the ventricles. Secrete CSF.

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 Types of Neurglia in the PNS
Schwann cells
Coat axons or form myelin sheaths around the larger nerve
fibers in the PNS.
 Vital to neuronal regeneration & electrical conduction.
 Protects the axon & electrically isolates it.
 Increases the rate of AP transmission.
Satellite cells
 Surround clusters of neuronal cell bodies in the PNS.
 Besides providing structural support, satellite cells
regulate the exchanges of materials b/n neuronal cell bodies
& interstitial fluid.
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 Neurons
Neurons are functional & structural
units of the NS.

A typical neuron has three distinct

functional parts: Cell body,
Dendrites (extend outward from the
cell body), & Axon.

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Neurons: Morphological Classification
Structurally neurons are classified into three types:
Uni-polar neurons
– Have cell body & only one projection w/c is either dendrite or
axon
– cell body found in the PNS, sensory in function
Bi-polar neurons
– Have cell body & two projections (dendrite & axon)
– A single axon & dendrite arise at opposite poles of the cell body
– Mainly found in the sensory neurons (retina, inner ear & in the
olfactory area of the brain).
Multi-polar neurons
– Are typical neural cells/single axon & many dendrites/
– Have cell body, an axon & several dendrites
– Cell body found in the CNS, motor in function 11
Figure: Morphological classification of neurons 12
 Functional Classification of Neurons
Three classes of neurons on the basis of their function are:
A. Sensory (afferent) neurons: conduct impulses from
periphery to the center/CNS/
B. Motor neurons (efferent): conduct impulses from CNS to
the periphery.
C. Interneurons/Association/Integrative neurons:
─ Conduct impulses from sensory area to motor area or
transmit nerve impulses b/n the sensory neurons & the
motor neurons.
─ Found exclusively in the CNS

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 Functional structures of Neurons
Neurons are specialized to
conduct information from one
part of the body to another.
There are many & different types of
neurons but most have certain
structural & functional characteristics
in common:
– Cell body (Soma)
– One or more specialized, slender
processes (axons/dendrites)
– Dendrites/Soma - an input region
– Axon - a conducting component
– Axon terminal - a secretory
(output) region
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 The Nerve Cell Body
An enlarged part of the nerve cell containing
abundant cytoplasm & cell organelles. It is
sometimes called the soma.
Receives information from dendrites & sends
messages out through the axon.
The primary site for maintaining the life of the
nerve cell w/c support the dendrites & axon.

15
 Cell Body (Soma)
Contains nucleus & most normal
organelles.
Biosynthetic center of neurons.
Contains a very active &
developed rough ER which is
responsible for synthesis of NTs.
The neuronal rough ER is
referred to as the Nissl body.
Contains many bundles of
protein filaments (neurofibrils)
w/c help maintain the shape,
structure, & integrity of the cell.
In the soma above, notice the
small black circle. It is the
nucleolus, site of ribosome
synthesis. The light circular
area around it is the nucleus.
The mottled dark areas
found throughout the
cytoplasm are the Nissl
substance. 16
 Somata, cont’d
Contain multiple mitochondria
Acts as a receptive service for
interaction with other neurons.
Most soma are found in the
bony environs of the CNS.
Clusters of soma in the CNS
are known as nuclei.
Clusters of somata in the PNS
are known as ganglia.

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Neuronal Processes
Axon:
Most neurons have a single
axon – a long (up to 1.5 m)
process designed to convey
info away from the cell body.
Originates from a special
region of the cell body called
the axon hillock.
Transmit APs (nerve impulses)
from soma to axon terminals
where they cause NT release.

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 The Axon

Axon can be either myellinated or unmyellinated

Very small in diameter, but can be very long (e.g. the
length of a leg).
Each nerve cell has only one axon.
Some cells have no axon termed as amacrine cells.
If an axon is cut, the distal portion degenerates due a
disruption of the cytoplasm extending from the cell body.

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Axon: Myelinated/Unmyelinated
Axolemma = axon plasma membrane

Surrounded by a myelin sheath, a

wrapping of lipid which:
– Protects the axon & electrically
isolates it.
– Increases the rate of AP transmission.
The myelin sheath is made by___???
in the CNS & by ____??? in the PNS.

This wrapping is never complete:

– Interspersed along the axon are gaps
where there is no myelin – these are
called nodes of Ranvier. 20
The Dendrite
An incoming nerve cell process that can act as a receptor
or connect to separate specialized receptors.
Conducts stimulus information to the nerve cell body
Produces voltage changes in response to various stimuli
& assists in nerve impulse formation.

The Axon Hillock

 The junction site b/n the nerve cell body & the axon.
 Processes voltage changes, or generator potentials (GPs)
from the dendrites & cell body, & assists the formation
of a transmittable nerve impulses.
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 Nodes of Ranvier
A Node of Ranvier is a space or gap found on a
nerve cell process (axon or dendrite) & is located
b/n the myelin sheaths formed by cells such as the
Schwann cell.
The exposed cell membrane located in the node can
facilitate the formation & transmission of nerve
impulses.
It is myelin free zone.

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 The Schwann cell

A specialized cell that supports & maintains

the fibers (axons & dendrites) of nerve cells in
the peripheral nervous system (PNS).
Contains myelin material
Assists in the repair & regeneration of fibers
Wraps around a section of a nerve fiber &
creates a protective myelin sheath.

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 The Myelin sheath
The axons of many neurons are myelinated, i.e., they
acquire a sheath of myelin, a protein–lipid complex that is
wrapped around the axon.
This whitish, fatty myelin material acts as an excellent
insulator & protector of the nerve cell fiber.
Outside the CNS, the myelin is produced by Schwann
cells, glia-like cells found along the axon.
The myelin sheath envelops the axon except at its ending
& at the nodes of Ranvier.
Not all mammalian neurons are myelinated; some are
unmyelinated.
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 Axon Terminals
Axon terminals are bulbous distal endings of the
many branches that extend from the end of an axon.
These bulb-like structures can also be called
synaptic knobs, buttons or even “end feet”

The axon terminal serves as a secretory component

that releases neurotransmitters in response to nerve
impulses

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 Membrane Potentials

Terms
Ion
Atom/molecule that have an electrical charge.
Anion
Negatively charged ion (e.g., Cl−).
Cation
Positively charged ion (e.g., Na+, K+, Ca2+).
Influx of ions
Flow of ions into the neuron.
Efflux of ions
Flow of ions out of the neuron.

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Anode
• Positive terminal of a battery.
• Negatively charged ions (e.g., Cl−) move toward an anode.

Cathode
• Negative terminal of a battery.
• Positively charged ions (e.g., Na+) move toward a cathode.

Electrical current
• Movement of electrical charge.
• Flow of current (I) depends on electrical potential and electrical conductance.
• Measured in amperes.

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Electrical potential (voltage)
• Difference in charge between the anode and the cathode.
• More current flows when this difference is increased.
• Measured in volts (V).

Electrical conductance
• Ability of an electrical charge to move from one point to another (g).
• Measured in Siemens (S).

Electrical resistance
• Inability of an electrical charge to move from one point to another (R).
• Measured in ohms (Ω).
• It is inverse of electrical conductance (R = 1/g.)

Ohms law (I = V/R, or V. g….)

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Direction of current flow
• Cations + anions carry electrical current.
• Current flow is defined as the direction of net movement of positive charge.
 Cations move in the same direction as the current.
Anions move in the opposite direction as the current.

Inward current
• Positively charged ions (e.g., Na+) flowing into the neuron.
Outward current
• Positively charged ions (e.g., K+) moving out of the neuron; or
• Negatively charged ions (e.g., Cl−) moving into the neuron.
Leakage current
• Current due to the flow of ions through the non-gated ion channels.
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Membrane Potential

4.1. Def.  electrical energy difference between the inside and outside
of the cell.

Em = Vin – Vout, where

Vin = Potential on the inside of the cell

Vout = Potential on the outside
Em = Membrane potential (mV)

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• Electrical potentials exist across the membranes of
virtually all cells of the body
• nerve and muscle cells, are capable of generating
rapidly changing electrochemical impulses at their
membrane
• Used to transmit signals along the nerve or muscle
membranes.
• Other cells glandular cells, macrophages, and
ciliated cells, local changes in membrane
potentials also activate many of the cells’ functions.
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• All cells have membrane potentials.

• Membrane potential  charge separation across the membrane.

• The Range of Em: -20 mV to -90mV

(organism, cell type).

• Any change of a membrane’s permeability of ions causes a change

in Em.

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Resting Membrane Potential
• Steady transmembrane potential of a cell that is not producing an
electrical signal.
• Always negative in nerve and muscle cells.
• Magnitude is κ for individual cell types.
o Nerve, cardiac and skeletal muscle: -55 to -90mV
o Smooth muscle: -55 to -30mV

33
• Inexcitable cells have RMP.
• RMP is necessary for the cell to fire an action potential.
• Resting membrane potential is nearly equals to that of EK.

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35
36
Determinants: Origins of Em
Passive determinants
Active determinant

Passive Determinants
A. Biochemical nature of plasma membrane of the cell.
Lipid bilayer (7nm = 60Å): Selective permeability
• Extracellular: +VE
• Intracellular: - VE

37
B. Asymmetrical/Unequal distribution of ions across the membrane

38
 Concentration of ions
Electrostatic
Inside Outside [ ] gradient pressure

Sodium (Na+) 12mM 145mM into cell into cell

Potassium (K+) 150mM 5mM out of cell into cell

Chloride (Cl-) 9mM 125mM in out

Calcium (Ca2+) 10-4mM 2.5mM into cell into cell

Organic anions: Fixed anions (Proteins, nucleotides, polyphosphates…)

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C. Leakage (Leak, non-gated, passive, resting) channels
• Leak K+ channels, leak Na+ channels, leak Cl- channels
• Leakage K+ channels are open at resting potential more than Na +, Cl-
• Resting membrane potential is nearly equals to that of the EK.

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D. Diffusional force

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Nernst Equation/Nernst Potential
Ion concentrations and equilibrium potentials:

i. Conc. of the ion inside and outside

ii. Temperature of the solution

iii. The valence of the ion

iv. The amount of work required to separate a given quantity of

charge.

Ex = RT ln [X]o
(mV) zF [X]I
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 Part I
Where
R = gas constant = 8.315jk-1mol-1
T = TKelvin = 271.16 + TCelcius

F = Faraday's constant = 96, 485 Cmol-1

z = Valence of the ion (+1, -1, +2)
[X]o = Concentration of the ion outside the cell
[X]i = Concentration of the ion inside the cell

NB. Nernst Equation predicts Equilibrium Potential (Eion).

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Goldman-Hodgkin-Katz Equation/The Constant field
Equation

• Polarity
• Permeability

• Concentration

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Goldman-Hodgkin-Katz Equation

1. The contribution of any ion to the Em is

determined by the membrane’s permeability
to that particular ion.

2. The higher the permeability of the membrane

to one ion relative to the others, the more
that ion will contribute to the Em.

3. The contribution of the impermeable ion to

the Em will be zero.
NB. GHK = predicts Resting Membrane of a cell.
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Active Determinant
Na+-K+-ATPase (Na+-K+ pump)
i. Features:

a. A carrier molecule uses the membrane-bound ATPase.

b. Primary active transport process (consumes ATP, pumps against conc.

or electrical gradient).

c. Operates as antiporter (coupled transporter):

Pumping 3Na+ out of the cell
Pumping 2K+ in (Electrogenic pump).

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ii. Location: Plasma membrane of virtually all animal cells.
200 Na+- K+-ATPase/RBC
35,000 Na+- K+- ATPase /WBC

iii. Functions

i. Maintenance of gradient of Na+ and K+ across the cell membrane

•Controls cell volume ( Na+ regulating osmotic forces)

ii. Control of membrane potential and excitability.

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• Na+ (outside): 14mEq/L
Na+ (inside): 14 mEq/L
• K+ (outside): 4 mEq/L
K+ (inside): 140 mEq/L
• The ratios of these two
respective ions from the
inside to the outside are
• Na+inside/Na+
• outside = 0.1
• K+inside/K+outside
=35.0

48
 Ion Channels
• When ion channels are open, they allow specific ions to
move across the plasma membrane, down their
electrochemical gradient–a concentration (chemical)
difference plus an electrical difference.
– Ions move from areas of higher conc. to areas of lower
conc. (the chemical part of the gradient).
– Also, positively charged cations move toward a negatively
charged area, & negatively charged anions move toward a
positively charged area (the electrical aspect of the
gradient).
– As ions move, they create a flow of electrical current that
can change the membrane potential.
49
 Ion Channels, cont’d
• Ion channels open & close due to the presence of “gates”.
– The gate is a part of the channel protein that can seal the
channel pore shut or move aside to open the pore.

• Electrical signals produced by neurons & muscle fibers

rely on four types of ion channels:
1. Leakage channels,
2. Ligand-gated channels,
3. Mechanically gated channels, and
4. Voltage-gated channels
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 Classification of Ion Channels
Na+ channels Ca2+ Channles
There are three major types:
1. Na+–leak channels There are three major types:
2. Voltage–gated Na+ channels 1. Voltage–gated Ca2+ channels
3. Ligand (chemical–gated) Na+
channels
with subtypes
2. Ligand–gated Ca2+channels
K+ Channels 3. G-protein–gated Ca2+ channels
There are four major classes:
1. K+–leak channels
2. Voltage–gated K+ channels
3. Ligand– gated K+ channels
4. G-prorein–gated K+ channels
51
 Ion Channels, cont’d

1. Leakage channels
• The gates of leakage channels randomly alternate b/n
open & closed positions.
• Typically, plasma membranes have many more
potassium ion (K+) leakage channels than sodium ion
(Na+) leakage channels, & the K+ ion leakage channels
are leakier than the Na+ ion leakage channels.
• Thus, the membrane’s permeability to K+ is much
higher than its permeability to Na+.

52
 Ion Channels, cont’d
2. Ligand-gated channel
• Opens & closes in response to a specific chemical stimulus.
• Chemical ligands (such as NTs, hormones), & particular
ions – can open or close this channels.
− E.g. Acetylcholine, opens cation channels that allow Na+
& Ca2+ to diffuse inward & K+ to diffuse outward.
3. Voltage-gated channel
• Opens in response to a change in membrane potential
(voltage).
• Participate in the generation & conduction of Aps.
53
 Ion Channels, cont’d
3. Mechanically gated channel:
• Opens or closes in response to mechanical stimulation in
the form of vibration (such as sound waves), touch,
pressure, or tissue stretching.
• The force distorts the channel from its resting position, &
opening the gate.
– Examples of mechanically gated channels are those found
in auditory receptors in the ears, in receptors that monitor
stretching of internal organs, & in touch receptors &
pressure receptors in the skin.

54
 Nerve Action Potential (AP)
Rapid transient change in RMP
AP is a short lasting event in which the electrical VM rises & falls rapidly
that occur in excitable cells.
It is very useful for cell-to-cell communication.
Nerve signals are transmitted by action potentials, which are rapid changes
in the membrane potential that spread rapidly along the nerve fiber
membrane.
Each AP begins with a sudden change from the normal negative RMP to a
positive VM & then ends with an almost equally rapid change back to a
negative VM .

55
 Stages of the AP
A. The Resting Stage
─ the RMP before the AP begins
─ is the polarized stage with -90 mV membrane potential
B. Depolarization Stage
─ initiated because of the rapid inflow of Na+ ions to inside,
creating positivity inside as the membrane permeability
increases to Na+ ions.
C. Repolarization Stage
─ initiated when the Na+ channels begin to close & the K+
channels open more than normal after few seconds, so that
K+ ions will diffuse rapidly to out & regains negativity.

56
 Generation of Action Potential
At rest, the voltage-gated Na+ & K+ channels in the
plasma membrane of a nerve cell are nearly closed & the
Na+/K+ pump moves 3Na+ ions to the ECF & 2K+ ions
to the ICF. This combination of activity contributes to
the formation of a RMP (-90 mV)

The negative state (-90 mV) of the ICF compared

to a positive ECF is due to the unequal flow of ions
across the plasma membrane

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Threshold potential
– The minimum initial depolarization caused by
threshold stimulation that will elicit an action
potential.( between +15 to +30 mV change)

58
 Generation of AP, cont’d
At rest, the ICF of an axon has a voltage about -90 mV (RMP)
When the membrane of the axon is properly stimulated, Na+
ions begin to leak into the ICF. This causes the voltage to
change to a less negative state.
When ICF voltage reaches a threshold of about -60mV, the
Na+ gates open.
As Na+ gates open, Na+ flow through Na+ channels increases
exponentially & quickly changes the voltage from a resting
level of -90 mV to +35 mV.
This rapid shift from a negative to a positive state is called
DEPOLATIZATION. At +35 mV, the Na+ gates close.
59
 Generation of AP, cont’d
When the Na+ gates close at +35 mV, the depolarization
process stops.
The +35 mV condition causes the K+ gates to open &
allows the K+ ions to flow from the ICF to the ECF.
The flow of K+ quickly reverses the potential from +35 mV
to -90 mV. This is called REPOLARIZATION.

60
61
62
Hodgkin-Huxley Expts, 1952
Squid Giant Axon

63
• Another means for studying the flow of
ions through an individual type of channel
is to block one type of channel at a time.
Tetrodotoxin, tetraethylammonium ion

64
 Generation of AP, cont’d
At the conclusion of each repolarization event, the
Na+/K+ pump moves the Na+ & K+ ions back to
their main storage areas & reset the membrane.

65
 Ionic Bases of AP
An immediate change of the RMP into depolarization that is
followed by reestablishment of the RMP (repolarization) is
called action potential or nerve impulse.
If RMP changes from -90 mV to threshold level (-75 mV) →
voltage gated Na+ channels open & → Na+ influx →
depolarization. Na+ channels become inactivated soon.
Opening of voltage gated K+ channels → K+ efflux →
repolarization.

66
 Ionic Bases of AP, cont’d
If VM reaches threshold, Na+
channels open & Na+ influx ensues
depolarizing the cell & causing to
↑ the VM. This is the rising phase
of an AP.
Eventually, the Na+ channel will
have inactivated & the K+ channels
will be open. Now, K+ effluxes &
repolarization occurs. This is the
falling phase.
– K+ channels are slow to open
& slow to close. This causes the -90 mv

VM to take a brief dip below

resting VM. This dip is the
undershoot, & is an example 67
of hyperpolarization.
• The movements of ions during the APs

Phases of AP:
1. Resting phase
2. Depolarization
3. Repolarization

68
 Na+ Channels

• They have two gates:

– At rest, one is closed
(activation gate) &
the other is open 1
( inactivation gate)
– Suprathreshold
depolarization affects
both of them

2
69
 Na+ Channels, cont’d

3 4

5
70
71
 Refractory period
The period of time after an AP begins during which an
excitable cell cannot generate another AP in response to a
normal threshold stimulus is called the refractory period
OR
During the time interval b/n the opening of the Na+ channel
activation gate & the closure of Na+ inactivation gate, a
Na+ channel cannot be stimulated.

There are two forms:

1. Absolute refractory period (ARP)
2. Relative refractory period (RRP)
72
 Refractory period, cont’d
A. Absolute Refractory Period /ARP/
─ A Na+ channel cannot be involved in another AP until
the inactivation gate has been reset.
─ A 2nd (another) AP can not be generated regardless of
the strength of stimulus.
─ ARP begins at the start of upstroke & extends into the
downward stroke.
─ During upstroke another AP can not occur b/c the
activated Na+ channels start as fast as possible. While
during the early portion of the downward stroke, AP can
not occur b/c Na+ channels are inactivated.
73
 Refractory period, cont’d
B. Relative Refractory Period/RRP/
− New AP can occur in an excitable fiber if the stimulus is
supra threshold (if the stimulus is sufficient/strong
enough).
− The stimulus should be greater than normal b/c there are
still inactivated Na+ channels & more K+ channels than
normal are still open.
− The RRP begins when the ARP ends.
Reasons
• Increased number of inactivated Na+ channels, and
• Activated K+ channels during RRP
74
 All-or-None Principle
Once an AP has been elicited at any point on the
membrane of a normal fiber, the depolarization process
travels over the entire membrane if conditions are right,
or it does not travel at all if conditions are not right. This
is called the all-or-none principle, and it applies to all
normal excitable tissues.

Occasionally, the AP reaches a point on the membrane

at w/c it does not generate sufficient voltage to stimulate
the next area of the membrane.

75
 Graded Potentials (GPs)
• A GP is a small deviation from the vM that makes
the membrane either more polarized (inside more
negative) or less polarized (inside less negative).
– When the response makes the membrane more
polarized, it is termed a hyperpolarizing GP.
– When the response makes the membrane less
polarized, it is termed a depolarizing GP.

76
 Graded Potentials, cont’d
• A GP occurs when a stimulus causes mechanically gated or
ligand-gated channels to open or close in an excitable
cell’s plasma membrane.
• Typically, mechanically gated channels & ligand-gated
channels can be present in the dendrites of sensory
neurons, & ligand-gated channels are numerous in the
dendrites & cell bodies of interneurons & motor neurons.
• Hence, GPs occur mainly in the dendrites & cell body of
a neuron.

77
 Graded Potentials, cont’d
• GPs have different names depending on w/c type of
stimulus causes them & where they occur.
– For example, when a GP occurs in the dendrites or cell
body of a neuron in response to a NT, it is called a
postsynaptic potentials
– On the other hand, the GPs that occur in sensory
receptors & sensory neurons are termed receptor
potentials and generator potentials

78
 Graded potential Vs. Action potential
Graded potential
1. Has graded responses-
Amplitude varies with condition
of the initiating event
2. Graded responses can be
summated
3. Has no refractory period
4. Is conducted decrementally,
amplitude ↓ with distance
5. Duration varies
6. Can be depolarization or
repolarization
7. Initiated by NTs, drugs,
hormones or spontaneously.
Action Potential
1. Membrane is depolarized to
threshold, amplitude is
independent of the initiating
event.
2. Action potential can not be
summated
3. Has refractory period
4. Not affected by distance
5. Duration is constant with a
specific cell under constant
condition
6. Is depolarization with an
overshoot
7. Initiated by membrane
depolarization. 79
Conduction of Action Potential (AP)
If an AP is generated at the axon hillock, it will travel all
the way down to the synaptic knob
The manner in which it travels depends on whether the
neuron is myelinated or unmyelinated

Unmyelinated neurons & muscle fibers undergo sweeping

/continuous/ conduction of an AP, whereas
Myelinated neurons undergo jumping /saltatory /
conduction of an AP

80
 Propagation
An AP can propagate itself across
the surface of the PM.
The depolarization caused by the
Na+ influx in one particular area of
the cell membrane causes opening
of the voltage-gated ion channels
in the adjacent membrane.
The resulting ionic influx then
causes voltage-gated channels to
open in the next area of membrane
& so on and so on. Thus the AP
propagates itself. 81
 Propagation of AP, cont’d
1. Sweeping/continuous/ conduction of AP:
– Occur in unmyelinated neurons
– The wave of depolarization & repolarization simply
travels from one patch (area) of membrane to the
next adjacent patch.
– Similarly, the AP moved in this fashion along the
sarcolemma of a muscle fibers.

82
 Propagation of AP, cont’d
2. Jumping/saltatory/ conduction of AP:
– Occur in myelinated neurons
– Saltare is a Latin word. Saltatory conduction meaning
“to leap.”
– The myelin sheath is not complete. There exist myelin
free regions along the axon, the nodes of Ranvier.
– Velocity is faster
– Economizes ATP

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Rates of AP Conduction Depends Upon
Rates of AP conduction depends upon:
• Level of myelination:
– Faster in myelinated than in unmyelinated
• Size of nerve fiber:
– Faster in large sized than in smaller ones
Age:
− Slower in babies & in elderly
− Maximum b/n the age 5-15 years
• Temperature:
– Axons propagate APs at lower speeds when cooled
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Calcium Ions
• The membranes of almost all cells of the
body have a calcium pump
• calcium serves along with (or instead of)
sodium
• calcium ions flow from the interior to the
exterior of the cell membrane
• creating a calcium ion gradient of about
10,000-fold.

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• In addition, there are voltage-gated
calcium channels.
• these channels are also called Ca++-Na+
channels.
• The calcium channels are slow ( 10 to 20
times as long sodium channels.
• numerous in both cardiac muscle and
smooth muscle.

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• Increased Permeability of the Sodium
Channels When There Is a Deficit of
Calcium Ions.
• The nerve fiber becomes highly excitable,.
• Fall of calcium 50 per cent below
normal causes spontaneous discharge
often causing muscle “tetany.”

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4. Action Potentials with Plateau
Plateau prolongs the period of depolarization

Reasons :

i. Fast channels: Voltage-gated Na+ channels  spike portion of AP

Slow channels: Voltage-gated Ca2+ channels (L-type) 

Ca2+-Na+ channels ↑ gCa2+  plateau

ii. Voltage-gated K+ channels: slow/delayed opening.

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Clinical correlates: Factors Affecting Excitability
1. Metabolic

a. pH : Acidosis  ↓ neuronal excitability (depression)

Alkalosis  ↑ neuronal excitability
2. Mechanical
a. Hypoxia: ↓ PO2  ↓ neuronal excitability
b. Pressure: ↓ Excitability  Conduction block
c. Ischaemia: ↓ Excitability  Conduction block

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3. Drugs and Chemicals

i.Caffeine (Coffee)  ↓ threshold ↑ neuronal excitability

ii.Theophylline (Tea): same mech.

iii.Strychinine  ↑ neuronal excitability

•Does not reduce threshold for excitation of neurons.
•Inhibits the action of the inhibitory transmitters on the neurons.
•Inhibits the effects of glycine in the spinal cord  effects of
excitatory transmitters become overwhelming  neurons discharge
repetitive discharge  severe tonic muscle spasms 
respiratory failure  death.
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iv. Anaesthetics: (Procaine, Lidocaine, Tetracaine, benzocaine)
•↑ Membrane threshold for excitation
• Synaptic transmission at many points in NS.
•Act on voltage-gated Na+ channels  closed state ↓excitability
v. Inorganic Ions
a.Na+ - free solution  no nerve impulse
b. K+: ↓ K+  ↓ excitability
↑K+  ↑ excitability
c. ↑ Ca2+  ↓ membrane permeability
(resists Na influx) ↓excitability
↓ Ca2+  ↑ permeability of Na channels  ↑ excitability

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vi. Temperature
•Warming  ↑ excitability
Cooling  ↓ excitability

vii. Toxins
a. Voltage-gated Na+ Channels
•Tetrodotoxin (TTX) :
•Saxitoxin (STX)
•Pronase
b. Voltage-gated K+ channels
•Tetraethyleammonium (TEA)
•4-Aminopyridine (4AP)

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 Synaptic Transmission
Synapse is the junction b/n two cells in which one
must be a neuron. It is the site of transmission from
one neuron to the next
There are two types of synapse:
Chemical, and
Electrical
One neuron will transmit impulse to another
neuron or to a muscle or gland cell by releasing
chemicals called neurotransmitters.

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Electrical synapse

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 Synaptic transmission, cont’d
There are 3 types of synapses
1. Neuroneuronal junction (presynaptic & postsynaptic
neurons)
2. Neuromuscular junction
3. Neuroglandualr junction
There 3 types of neuroneuronal junctions
(Axo-dendritic, axosomatic & axo-axonic junctions)
Components of synapse
1. Presynaptic terminal contains neurotransmitter (NT)
2. Synaptic cleft contains ECF & enzymes
3. Postsynaptic neuron contains receptor for action of NT
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Neuro-neuronal & Neuromuscular junctions

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Neuro-neuronal synapse

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Chemical Synaptic Transmission

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Mechanism of Chemical Synaptic Transmission
An AP reaches the presynaptic axon terminal of the
presynaptic cell & 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 & then bind to
specific receptors on the postsynaptic membrane &
initiate postsynaptic APs.
NT-receptor interaction results in either EPSP or IPSP.

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 Mechanism of Chemical Synaptic…..
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

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Excitatory & Inhibitory Synapse

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 Neurotransmitter Removal
Why do we want to remove
ACh from the NMJ ?

How was ACh removed from

the NMJ ?

NTs are removed from the

synaptic cleft via:
– Enzymatic degradation
– Diffusion
– Reuptake
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 Properties of synaptic transmission
1. Unidirectional conduction
2. Synaptic delay: 0.5 -1.0m/s
3. Fatigue: ↓ in response of postsynaptic neurons after
repetitive stimulation by the presynaptic neurons.
4. Synaptic potentiation (facilitation): persistence of output
signals after the stoppage of input signal.
 Synapse is a target for the action of several groups of
drugs
 Caffeine, theophylline, theobromine: ↑ Synaptic transmission
 Hypnotics, anesthetics, tranquilizers: ↓ Synaptic transmission

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 Classes of Neurotransmitters
Classes Neurotransmitters Receptors Distribution &
Role
I Acetylcholine (Ach) Nicotinic receptors Excitatory in
Muscarinic receptors CNS, PNS
II Adrenaline, nor-adrenaline α and β adrenoreceptors Excitatory
Amines Dopamine Dopaminergic Rs: A, B Inhibitory in BG
Histamine Histaminergic Rs: H1,H2 Excitatory
III GABA (γ-amino butyric acid) GABA-A & B receptors Inhibitory in BG
Amino Glycine Glycine receptors Inhibitory
Acids Aspartate NMDA receptors Excitatory
Glutamate NMDA receptors Excitatory
IV Hypothalamic hormones, Hormone receptors Stimulatory or
Polypep pit. hormones, ANG-II inhibitory
V Nitric oxide Memory
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Net effect of inputs depends on the location/proximity, size, and shape
of the synapse:
• Synapses on cell bodies: inhibitory
• Synapses on dendritic spines: excitatory.
• Synapses on axon terminals: modulatory.
Net effect is algebraic sum of excitatory + inhibitory signal inputs.

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Synaptic Integration: Summation
• Temporal
• Spatial

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Temporal summation
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Spatial summation
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8. If excitatory signals > inhibitory signals → depolarization/excitatory.

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9. If inhibitory signals > excitatory signals → hyperpolarization/inhibitory.

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The Physiology of Synaptic Transmission
The synaptic integration Part II

10. Action potential is initiated at the initial segment, axon hillock.

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The Physiology of Synaptic Transmission
The synaptic integration Part II

EPSP + IPSP = GPSP

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The Physiology of Synaptic Transmission
The synaptic integration Part II

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 Clinical correlation
• The Ach receptor is specifically bound by
snake venom components (alpha-
bungarotoxin and cobratoxin)
• Benzodiazeprine drugs (Valium and
Librium) enhance the effects of GABA

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Docking proteins
(synaptotagamin,synaptobrevin)
The docking process is blocked by
neurotoxins such as
syntaxin
 tetanus toxin (in the spinal cord)
and botulinum toxin (in the motor
neurons).
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