Nerve

Physiology
By Dr Adeela Shahid
Professor of Physiology
SMDC

Objectives

At the end of lecture 1st year MBBS

student should be able to:
Discuss the physiological
anatomy of Nervous tissue
Discuss the Axonal Transport

Nervous Tissue is
composed of two type
of cells
Neurons
Neuroglial

cells

Neurons/ Nerve Cell

Neuron

is a nerve cell with all

its processes.
It is the basic structural and
functional unit of nervous
system
Cannot divide by mitosis

 Ability

to respond to stimulus &

convert it into an action potential
It Produces and conduct
electrochemical impulses
Communicate with other neurons at
synapse
Release chemical regulators

Nerve
Cable

like bundle of peripheral axons

located outside CNS
Most

composed of both motor and

sensory fibers

In

the CNS axons form tracts

Structure of a
Neuron
Cell Body / Soma
Dendrites
Axon (Nerve Fiber)

Neuron

Neurons

(continued)

Cell Body (Soma)

Cell

bodies within CNS clustered into

nuclei, and in PNS in ganglia
Located in gray matter of CNS or in
the ganglia
Shapes
Satellite
Rounded
Pyramidal
Fusiform

Cell Body

Cell body
Has a nucleus with one or two nucleoli but
no centrosome. Lost the power of division.
Cytoplasm
Organelles
Mitochondria, ER, Ribosomes,
Lysosomes, Golgi Apparatus
Nissl bodies / Nissl granules
Composed of endoplasmic reticulum
with abundance of ribosomes. It is the
site of protein synthesis

 Neurofibrils
Neurotubules

& neurofilaments
Melanin, cu, Iron
Lipofuscin
Yellow brown granular pigment
composed of lipid containing
residues of lysosomal digestion
which accumulate as the neuron
ages.

Nissl Bodies

 Two

kinds of processes
Dendrites
Axon

Dendrites

They are usually short, tapering and

highly branched. Dendrites extend
from the cell body.
Receiving or input portion
Provide receptive area.
Transmit electrical impulses to cell
body.
Cytoplasm contains Nissl bodies
,mitochondria & other organelles.

Axon

Axon is a long thin cylindrical projection that originates from thickened cone
shaped elevation called Axon hillock.
The part of the axon closest to the axon hillock is called Initial segment. It is
highly excitable.

Axon contains mitochondria, microtubules & neurofibrils but no RER or

nissle bodies. Has Axoplasm and Axolemma

AXON
Axon

divides into pre-synaptic

terminals each ending in a
number of synaptic knobs also
called terminal buttons
Carry the impulses away from
the cell body towards another
neuron, muscle or a gland.

Motor Neuron with a

Myelinated Axon

Axonal Transport
Axonal

transport
Movement of materials from or to the
cell body by axoplasmic flow is called
axonal transport.
Types of flow
Orthograde Flow
Retrograde Flow
Axonal transport uses two molecular
motors DYNEIN and KINESIN and
transport occurs along microtubules.

Axonal Transport along

Microtubules by Dynein and
Kinesin

Orthograde Transport
Movement toward the synapse is called
anterograde /orthograde transport.
Proteins and polypeptides are
transported to the axonal endings by
Axoplasm flow.
Fast axonal transport 400mm/day
Slow axonal transport 0.5-10mm/day

Retrograde Transport
Movement

toward the cell

body is called retrograde
transport 200mm/day.
Retrograde Flow: nerve
growth factors, tetanus
toxins, viruses (Polio) and
used up synaptic vesicles.

Coverings of Axon
Axolemma
Myelin

sheath
Neurilemma
Outermost transparent
cell membrane of
shawann cell.

Endoneurium
CT which surround the Neurilemma
Perneurium
Bundles of nerve fiber surrounded
by CT
Epineurium
Many Bundles bounded together by
CT

Objectives

At the end of lecture 1st yr MBBS student must be

able to:

Describe the importance of nodes of Ranvier

Differentiate between myelinated and
Unmyelinated fibers
Elaborate the process of myelination
Classify neurons
Enumerate the neuroglial cells and their function
Define stimulus & enumerate types of stimulus
Define action potential

Nodes of Ranvier:

Physiologic Importance of
Nodes

Nodes of Ranvier:
Periodic constrictions that are about 1mm
apart are called nodes of Ranvier
Unmyelinated areas between adjacent
Schwann cells
Produce nerve impulses
Important for exchange of ions between the
interior of axon & the external environment.

Nerve fibers lying in PNS

Myelinated

nerve fibers
Unmyelinated nerve fibers

Nerve fibers in PNS

Enveloped by Shawann
cells
Schwann cells:
Successive wrapping
of the cell membrane
forms myelin sheath
Provide insulation.
Provide structural &
nutritive support
Repair nerve fiber after
damage

Myelination
Nerve fiber invaginate the Shawann cell
Point of fusion of Shawann cell
membrane with nerve fiber is called
Mexacon.
Mexacon wraps around the axon in a
spiral manner.
Axon surrounded by several layers of
shawann cell membrane form myelin
sheath. No cytoplasm (white in color)
This process is called myelination

Myelination

Outermost membrane of this sheath

is called the neurilemma.

Each lamella is a lipid bilayer

Provides insulation prevent ionic

fluxes across the membrane of axon

Myelination

Myelination

Unmyelinated Nerve Fibers

in PNS
Nerve fibers of small diameter.
Only Mexacon is formed no myelin
sheath is formed, it contain
cytoplasm of shawann cell.
Fibers conducting pain sensation
& of ANS

Nerve Fibers Lying Within

the CNS
Myelinated

nerve fibers

Unmyelinated

fibers

Myelinated Nerve Fibers

Oligodendrocytes
Each has
extensions that
form myelin
sheaths around
several axons.
Insulation.

Un-myelinated Nerve
Fibers
Supported

by mass of
surrounding tissues.

Functions of Myelin
Sheath
Provides

insulation

Support
Nutrition
Increases

the speed at which

nerve impulse is propagated in
myelinated nerve fiber.

Composition of Myelin
sheath
The

dry mass of myelin

sheath is about 70 - 85%
lipids
15 - 30% proteins

CLASSIFICATION
OF NEURONS

Classification of Neurons
Structural/Histological classification
Functional/Physiological
classification
Classification according to the size
Classification according to the
location

Structural/Histological
classification.

Uni-polar

Have one process,

different segments
serving as dendrites &
axon (Invertebrate
neuron)

Psuedo-unipolar

Both the dendrites &

axon arise from a
common stem that
divides into 2 processes
(sensory neurons).
neurons

Structural/Histological
Classification

Bi-polar

Dendrite & axon

arising at different
sites from the cell
body.
Retina
Multipolar
Have several dendrites
arising from one pole &
axon arising from
opposite pole.
Brain & spinal cord

Functional/Physiological
classification

Motor neurons / Efferent neurons

Carry signals from CNS towards periphery
(effectors) muscles & glands
Alpha-Motor Neurons
Gamma-Motor Neurons
Sensory neurons / Afferent neurons
Carry impulses from periphery towards CNS.
Interneurons / Association neurons
Connecting neurons located in the CNS connect
sensory & motor neurons.

Functional Classification of
Neurons

Classification according to
the size
Golgi type-1-neurons
Have a very long axon found in
brain.
Golgi type-2-neurons.
Have small thick, plump axons
found in spinal cord

Classification According to
the Location
Upper motor Neurons
Brain
Lower motor neurons
Cranial nerve nuclei in brain.
Spinal cord
Alpha & Gamma Motor Neurons
in the anterior horn of spinal cord

NEUROGLIA
/SUPPORTING CELLS

Neuroglia /Supporting
Cells

The different types of

neuroglial cells

Astrocytes
1.
2.

3.

4.
5.
6.

Supporting cells
Nutritive Function
End feet of astrocyte surround capillaries
take up glucose from the blood
Take up some neurotransmitters released
from the axonal terminals of neurons.
Blood Brain Barrier (BBB)
Phagocytosis
Healing

Astrocytes have processes

that end on capillaries and
neurons

Neuroglial Cell

(continued)

Oligodendrocytes
Form myelin sheath around nerve fibers in
CNS.
Microglia Cells
Phagocytic cells, remove debri resulting from
injury, infection, and disease (eg, multiple
sclerosis and Alzheimer disease).
Satellite Cells
Surround cell bodies in ganglia, provide
support & nutrition to cell bodies
Schwann Cells

Membrane
Potential
Dr Adeela Shahid
Professor of Physiology
SMDC

Objectives

At the end of lecture 1st yr MBBS student

should be able to:
Elaborate the concept of membrane
potential
Explain the Physiological basis of
membrane potential
Explain diffusion potentials of Na & K
Define Nernst potential

Membrane Potential
It is the separation of opposite
charges across the membrane.
OR
Difference in the charges across
the membrane.

Membrane Potential
caused by Diffusion

Diffusion Potential Caused by

Concentration difference of Ions on
the two sides of the Membrane.

Proteins and PO4 are negatively charged at

normal cellular PH
These anions attract +vely charged ions that can

Potassium Diffusion /
Equilibrium potential

If K+ is the only ion able to diffuse

through the membrane, it would
distribute itself between the I/C and
E/C compartments until an equilibrium
is established.

Membrane Potential caused by

K Diffusion
Due to the concentration
gradient K+ moves out.
Outside becomes +ve
Membrane is impermeable
to -ve Anions.
Inside becomes ve.
Electrical force starts
pulling K+ back into the
cell.

No further movement of K+
occurs when the inward electrical
force /electrical gradient pulling
the K ions inside exactly counterbalances the outward force of
diffusion/ concentration gradient.
The MP at this point is called
equilibrium potential for K+
The potential difference is 94 mv
with negativity inside the fiber
membrane.
Diffusion Potential is -94 mv

Potential difference 94 mv, if K+ is the only

diffusible ion.
EK+ = -94 mv
When the Diffusion & Electrical forces are equal and
opposite to each other net movement of K+ ceases.

Membrane potential caused by

Na+ diffusion
High concentration of Na
outside
Na moves into the cell.
Inside becomes +ve.
Outside -ve inside.
Electrical gradient tends
to move Na + out of the
cell.

When the outward electrical

gradient counterbalances the
inward concentration
gradient no further
movement of Na occurs.
Diffusion Potential is 61mv
with positive inside the fiber.
Equilibrium potential for Na
ENa+ = +61mv potential will
blocks further movement of
Na ions from outside to
inside.

Equilibrium Potentials

Equilibrium Potential for Potassium

is
-94mv
Equilibrium Potential for Na is
+61mv

Membrane Potential caused

by Diffusion of K ions
Membrane potential is in large part
determined by K ions
Why K+ spontaneously diffuses
outward.
Membrane more permeable
Hydrated forms of K are smaller
K+ gradient 30 times more inside

Nernst Potential
The

potential across the

membrane that exactly opposes
net diffusion of a particular ion
through the membrane is called
Nernst Potential.

Nernst Potential
Magnitude is determined by the
ratio of concentration of the ion on
the two side of the membrane.
The greater this ratio, the greater
the tendency for the ion to diffuse
in one direction, and therefore the
greater the Nernst potential
required to block net diffusion.

Nernst equation

Used to calculate the Nernst

potential for any univalent ion at
normal body temperature:

Nernst Potential
Nernst potential is the potential inside the
membrane. Potential in the ECF outside
the membrane remains at zero potential.
If a positive ion is diffusing from outside
to inside the sign will be +ve.
If positive ion is diffusing from inside to
outside the sign will be ve.
SIGN Indicates the polarity of the excess
charge inside of the membrane.

Outside

Inside

Na

142 mEq/L 14 mEq/L

4 mEq/L

140 mEq/L

Calculation
Nernst potential for K
Concentration of K+ inside the cell is
greater than outside (140 mEq/L inside
compared to 4 mEq/L outside)
K+ inside/ K+ outside = 140/4= 35
Log of 35 is 1.54
61 x 1.54 = 94
Nernst Potential will be -94 mv

Nernst potential for Na

The concentration of Na+ in the
extra cellular fluid is 142 mEq/L,
whereas its concentration inside cells
is only 14 mEq/L
Na+ inside/ Na+ outside = 14/142
Na+ inside/Na+outside = 0.1
?

Objectives

At the end of lecture 1st yr MBBS

student should be able to:
Explain the importance of Goldman
equation
Explain diffusion potentials of Na &
K
Discuss resting membrane potential

Diffusion Potential due to several

ions

If membrane is permeable to several

ions diffusion potential depends upon:
Concentration

of each ion inside &

outside
Permeability of the ion
Charge of each ion

Goldman equation

Goldman equation, or the

Goldman-Hodgkin-Katz

Gives the membrane potential on the inside

of the membrane
When 2 univalent +ve ions
Sodium (Na+) and potassium (K+)&
When 1 univalent -ve ion
chloride (Cl) are involved

Goldman equation
1.

2.

3.

Na+, K+, and Cl- ions are important ions

involved in the development of membrane
potentials in nerve and muscle fibers.
Concentration gradient of each ion is
important in determining the membrane
potential.
Permeability of membrane for a particular
ion is very important in determining the
membrane potential. If membrane
permeability is 0 for Na & Cl then MP will be
equal to the Nernst potential for K.

4. Positive ion concentration gradient or the

movement from inside to outside causes

negativity inside the membrane e.g K + ions.
Negative ion gradient or movement from
outside to inside causes negativity inside e.g.
Cl- ions.
5. Permeability of the Na & K channels
undergoes rapid changes during transmission
of a nerve impulse, whereas the permeability
of Cl channels does not change. Rapid
changes in Na & K permeability are primarily
responsible for signal transmission in
nerves.

Resting
Membrane
Potential

Resting Membrane
Potential of Nerves
Potential difference across the
membrane at rest is called resting
membrane potential.

OR
The membrane potential of a cell that is
not producing impulses is called RMP.
The Potential at rest is called RMP.

RMP
Large nerve fiber
Neuron cell body
SA node
mv
Skeletal muscle

-90 mv
-70 mv
-55 to -60
-90 mv

RMP
RMP exist because of a build up of
ve charges on inner side of the
membrane & an equal buildup of
+ve charges on the outer side.
Such separation of +ve & -ve
charges have potential energy
measured in mv.
Greater the difference in the charges
greater would be the potential.

1.
2.
3.

Origin of Normal
RMP
Contribution of the K Diffusion Potential
Contribution of the Na Diffusion Potential
Contribution of the Na-K Pump
OR
K+ leak channels
Na+ leak channels
Na+/ K+ pump

Origin of Normal
RMP

Contribution of K
diffusion

K+ outside: 4 mEq/L
K+ inside: 140 mEq/L
K+inside/K+outside = 35.0
Nernst potential of K=-94mv

Contribution of Na
diffusion

Na+ outside: 142 mEq/L

Na+ inside: 14 mEq/L
Na+inside/Na+outside = 0.1
Nernst potential of Na
=+61mv

A = RMP due to K diffusion alone

B =RMP due to both Na & K

Diffusion of Na- K Ions, & NaK Pump

How do these interact with

each other to get RMP of -90
mv ?

Using the Goldman equation

Membrane is highly permeable to
potassium it is 100 times more permeable.
Outward K diffusion contributes mainly to
RMP.
Goldman equation gives a potential inside
the membrane of 86 mv, which is near
the potassium potential (-94 mv)

RMP = -90 mv
-86

is due to Na & K
diffusion.
-4 is due to Na/K pump

RMP

The actual value of the RMP

depends on two factors:
1. The ratio of the concentrations
of each ion on the two sides of
the membrane.
2. The specific permeability of the
membrane to each different ion.

Measurement of Membrane
Potential

Membrane potential of Nerve

Fiber
Distribution of positively
and

negatively charged ions in the

ECF surrounding a nerve fiber
and in the fluid inside the fiber
Negative charges along the
inside of the membrane
Positive charges along the
outside surface.
The lower picture shows the
abrupt changes in membrane
potential that occur at the
membranes on the two sides
of nerve fiber

Evidences
Change the concentration of K + in ECF
causes disturbance of RMP
In Hyperkalemia Membrane potential
becomes less negative (decrease in RMP) &
membrane becomes hyper excitable. i.e. early
depolarization.
lethal injections of KCl (raising the extra
cellular K+ concentrations and depolarizing
cardiac cells.).
In Hypokalemia there will be increase in RMP.

Objectives

At the end of the lecture 1st yr MBBS student

should be able to:
Define action potential
Enumerate the phases of action potential
Explain the phases of action potential
Explain the ionic basis of action potential

ACTION
POTENTIAL

Stimulus
Any change in the external environment that
is strong enough to initiate an action potential.
Types
Electrical
Chemical
Hormonal
Thermal
Mechanical
Electromagnetic Radiation

Levels of Stimulus
Subthreshold
Threshold
Suprathreshold

Action Potential / Nerve

Impulse
It is a self propagating wave of
electro negativity that passes along
the surface of the axolemma.
OR
It is a abrupt pulse like change in
the membrane potential lasting for
fraction of a second.

Action Potential
A

sequence of rapidly occurring

events that reverse the
membrane potential & then
restore it to the resting state.

Action Potential
It

is a large change in
membrane potential from a
value of -90/-70mv to a peak
of about +35mv & back to
-90/-70mv.

 Action

potential is generated at
the axon hillock where density of
voltage gated Na channels is
greatest.

Duration

varies e.g. 1-2 msec in

nerve fibers, 2-4 msec in muscle
fibers, 200-300 msec in heart.

Action Potential
It begins when signals from the dendrites &
cell body reach Axon Hillock & causes
membrane to depolarize.
As the Axon Hillock depolarizes the voltage
gated channels for Na open rapidly
increasing membrane permeability to Na.
In action potential there is reversal potential .
Inside becomes +ve
Outside becomes ve

Phases
Resting

Membrane
Potential
Depolarization
Repolarization
Hyperpolarization

PHASES OF ACTION
POTENTIAL
Resting Membrane
Potential
Stimulus Artifact
Latent Period
1. Initial Depolarization/Slow Phase
2. Threshold level / Firing level
3. Rapid Depolarization
4. Over shoot potential
5. Rapid Repolarization
6. Slow after Depolarization/negative after potential
7. Hyperpolarization / Positive after potential

-65

6
-90
7

Resting stage
Before

action potential
begins, the membrane is in
resting stage & is said to be
polarized because of -90mv
RMP.

Stimulus artifact
When

the stimulus is applied, there is

a brief irregular deflection of the
baseline, which is called stimulus
artifact.
This artifact is due to current leakage
from the stimulating electrodes to the
recording electrodes.

Latent Period
The

stimulus artifact is followed by

an iso-potential interval called
latent period.
The time period between
application of stimulus to the onset
of action potential is called LATENT
PERIOD.

-65

6
-90
7

Initial Depolarization/Slow
Phase
The

stimulus
causes opening of
some Na channels
resulting in initial
20mv 25mv
depolarization.

FIRING LEVEL

The stimulus at which

enough voltage gated
Na channels open is
called Threshold
stimulus or that level
is called FIRING
LEVEL.
There is rapid
opening of the
voltage-gated Na
channels.

Rapid Depolarization

Large no of Voltage-gated Na channels open up

Open fast, close fast
Large numbers of +vely charged Na ions moves
inside.
Loss of negativity inside the membrane.
Inside becomes +
The normal polarized state of 90 /-70mv is lost
by the inflowing +vely charged Na.
The potential rising rapidly in the +ve direction.
This is called depolarization . Activation gates
remain open for a fraction of millisec, then
become inactivated this is the end of
depolarization.

Inactivation gates
never open once
closed unless
membrane
potential becomes
near the RMP
(Threshold).
Inactivation of Na
gates at +35mv
open K gates
Slow to open &
slow to close

-65

6
-90
7

Overshoot
Potential
The Action
Potential curve
reaches the zero
potential rapidly
& then
overshoots the
zero line up to
+35 mv.

Rapid Repolarization
Stage
K gates open slowly &
K gates open slowly &
K moves out
K efflux continues
Inside becomes -Ve
Return of negativity
inside the membrane.
This re-establish the
normal RMP. This is
called Repolarization

Spike Potential
The

phase of rapid rise of

potential in depolarization
phase & rapid fall in
Repolarization phase is called
Spike Potential

Slow After Depolarization/

Negative after potential

The slow repolarization phase which

follows a rapid fall in spike potential
untill RMP is achieved.
When repolarization is 70% complete
its down stroke is slowed.
K accumulates on the outer surface
which slows down further K efflux.

-65

6
-90
7

Hyperpolarization/
Positive
After
Potential
When potential has

reached base line it

becomes more ve than
the normal RMP for few
millisec after action
potential is over this is
called Hyperpolarization.
Many K channels remain
open for several millisec
after repolarization of
membrane is complete.

Phases

Resting Membrane Potential

Stimulus Artifact
Latent Period
Initial Depolarization/Slow Phase
Firing level / Threshold level
Rapid Depolarization
Rapid Repolarization
After Depolarization
Hyperpolarization/Positive after potential

Objectives

At the end of lecture 1st yr MBBS

student should be able to:

Explain the ionic basis of Every phase of

action potential
Discuss the role of Ca & other ions in
nerve excitability

Ionic Basis of Action

Potential
RMP
At -90 mv, outside the membrane is
+vely charged & inside is vely
charged.
More Na Outside & more K inside .
Initial Depolarization .
When stimulus is applied Permeability
for Na slowly increases till it reaches
FIRING LEVEL.

Changes in Na and K
conductance during Action
Potential

Ionic Basis of Action

Potential (cont)

Depolarization Phase
At threshold stimulus there is
sudden opening of large number of
Na channels. Na moves in resulting
in depolarization up to +35mv.
Na channels are inactivated & Na
gates close at +35mv.

Ionic Basis of Action

Potential (cont)

Rapid Repolarization Phase

Na gates are inactivated but K gates
open at +35mv & K efflux continues
Carrying positive charges to the outside.
Inside becomes ve & outside becomes
+ve.
Slow Repolarization /Slow After
Depolarization
After initial rapid fall/repolarization there
is slow fall. It is due large number of K
ions which accumulates outside.

Hyperpolarization /
Positive After
Potential
Slow

efflux of K continues even

after the RMP is reached
resulting in Hyperpolarization

Role of other Ions during Action

Potential

Impermeant Negatively Charged Ions

(Anions) Inside the Nerve Axon.
Anions of protein molecules, organic
phosphate compounds and sulfate
compounds.
Calcium Ions.
calcium pump
voltage-gated Na-Ca channels.
Ca channels are numerous in both cardiac
muscle and smooth muscle.
Increased Permeability of the Na Channels when
there Is a deficit of Ca Ions.

Role of Calcium Ions in

Excitability

Ca ions stabilizes the membrane.

Ca ions from ECF bind with outer surface of
Na Channels & results in complete closure of
activation gates at rest.
In HYPOCALCEMIA there wont be complete
closure of gates. Threshold level decreases &
Na will move in resulting in excitation.
Nerve fibers are hyper-excitable in
Hypocalcemia leading to TETANY

Evidences
Changing the concentration of K+ in ECF
there is disturbance of RMP
In Hyperkalemia Membrane potential
becomes less negative & membrane becomes
hyper excitable. i.e. early depolarization.
lethal injections of KCl (raising the extra
cellular K+ concentrations and depolarizing
cardiac cells.).
In Hypokalemia membrane will become
more Ve

Threshold for Initiation of

the Action Potential

A sudden rise of 15 to 30 mv, in the

membrane potential in a large nerve
fiber from 90 mv up to about 65
mv usually causes the explosive
development of an action potential.
This level of 65 mv is said to be the
threshold for stimulation.

Initiation of Action
Potential

What initiates the action potential?

A Positive-Feedback Vicious Cycle Opens
the Sodium Channels.
Any stimulus which causes initial rise in the
membrane potential from 90 mv toward the
zero level, the rising voltage itself causes
many voltage-gated Na channels to open. This
allows rapid movement of Na ions ,which
causes a further rise in the membrane
potential, thus opening still more voltagegated sodium channels

Properties of Action
Potential

It is Sudden & abrupt in onset.

Self propagated
It is of limited amplitude & magnitude.
Short duration
Obeys all & none law
Action

potentials either occurs maximally

or they do not occur at all.

Has a refractory period

APPLIED
PHYSIOLOGY OF
ACTION POTENTIAL

Objectives

At The end of lecture 1st yr MBBS

student should be able to
Applied Physiology of Action potential
Discuss Voltage clamp
Define Refractory period
Enumerate the types of refractory
period

Local
Anesthetics
Procaine
Tetracaine
Lidocaine

Local Anesthetics
Block

voltage gated Na channels.

Act directly on the activation gates of the
sodium channels
Prevent them from opening in response to
stimulus.
In response to cut or injury the pain signals
generated in the periphery cannot reach
the brain and cannot give rise to sensation
of pain.

Voltage Clamp
It

the apparatus used to

Measure the effect of
voltage on opening and
closing of the voltage
gated channels

Measure voltage
of
membrane
potential

conduct electric
current

To study the glow of ions through a

singal channel is to block one type of
channel
Tetrodotoxins
Toxin produced by the ovary of a puffer
fish, binds to voltage gated Na channels.
When applied to the exterior of nerve
fiber it will block the Na channels.
Tetraethylammonium ion
Blocks the K channels when applied to
the interior of the nerve fiber.

Periods of Action
Potential
Latent

Period
Refractory Period
Absolute Refractory
Period
Relative Refractory
Period

Refractory Period
It

is period during which a

nerve fiber either does not
respond or may responds to a
stimulus of threshold level or
suprathreshold level.

Types of Refractory
Period
Absolute

Refractory Period

(ARP)
Relative Refractory Period

Absolute Refractory
Period (ARP)
The

absolute refractory period

is that period during which
second action potential can
not be generated no matter
how strong the stimulus is.

The ARP is due to inactivation of Na

channels.
Nerve fiber looses its excitability.
Rapid depolarization & 2/3 of the
repolarization.
Length of this period determines
the frequency of action potentials.
The shorter the ARP, the greater
the frequency.

Relative Refractory
Period
The relative refractory
period is that period
during which a
greater than normal
strength of stimulus
is required to produce
second action
potential.
It is due to continuous
K efflux.

Objectives

At The end of lecture 1st yr MBBS

student should be able to

Explain transmission of nerve

impulse in myelinated and
Unmyelinated nerve fibers

PROPAGATION OF THE
ACTION POTENTIAL

Propagation of the Action

Potential
The depolarization process travels along the
entire length of the fiber.
Direction of Propagation.
Action potential travels in all directions
away from the stimuluseven along all
branches of a nerve fiberuntil the whole of
the membrane is depolarized.
This

transmission of the depolarization

process along a nerve fiber is called a
nerve impulse.

PROPAGATION OF THE ACTION

POTENTIAL IN UN-MYELINATED
NERVE FIBER

Unmyelinated Nerve Fibers

In Unmyelinated
Nerve Fibers
conduction is
point to point.

Local circuits of
current develops
between
depolarized
point & adjacent
resting areas.

Propagation of the Action

Potential in Un-Myelinated
Nerve Fiber

Current flowing out of the

depolarized point will
open Na gates at polarized
point on the membrane &
action potential will appear.
Action potential elicited at
any one point on an
excitable membrane
usually excites adjacent
portions of the membrane.

Propagation of the Action

Potential in Un-Myelinated Nerve
Fiber

Newly depolarized areas produce

still more local circuits farther along
the membrane, causing more and
more depolarization resulting in
propagation of the action potential
along the membrane.

Conduction of Action Potential in

Myelinated Nerve Fibers/ Saltatory
Conduction

Myelin Sheath is
interrupted by nodes of
Ranviers.
All Channels are present
along the node of
Ranvier.
Action potentials only
occur at nodes.
Action potential/nerve
impulse jumps down the
fiber from node to node.

Significance
Fast conduction of action potential. (5-50
times more conduction velocity).
Less energy expenditure due to less ionic
changes. Ionic fluxes are occurring only at
nodes & no change is occurring at internodes.
Due to insulation by myelin sheath at the
internodal area there is decrease in
membrane capacitance which allows
repolarization to occur with very little transfer
of ions at the nodes of Ranvier.

Objectives

At The end of lecture 1st yr MBBS student

should be able to:
Explain the safety factor for
transmission of nerve impulse
Discuss Orthodromic and Antidromic
conduction of nerve impulse
Enumerate the properties of nerve fibers

Propagation of the Action

Potential

Safety Factor for Propagation of nerve

impulse.
If AP reaches at a point on the membrane
where it does not generate sufficient voltage to
stimulate the next area of the membrane the
propagation of depolarization stops.
The ratio of stimulus (for action potential) to
threshold for excitation must be greater than 1.
This greater than 1 requirement is called the
safety factor for propagation.

When excitability has been

reduced so low by local
anesthetic the ratio of strength of
action potential to threshold for
excitability (called the safety
factor) is reduced below 1.0,
nerve impulses fail to pass along
the anesthetized nerves.

ORTHODROMIC & ANTIDROMIC

CONDUCTION

An axon can conduct in either direction. When

an action potential is initiated in the middle of
it, two impulses traveling in opposite
directions.
Orthodromic conduction
From synaptic junctions or receptors away
from soma along axons to their termination.
Antidromic Conduction
Conduction in the opposite direction
towards the cell body is called antidromic
conduction

Physiological Properties of
Nerve Fibers

Excitability
Conductivity
All or None Law
Refractory Period
Absolute Refractory Period
Relative Refractory Period
Strength Duration Curve

Excitability
When

a nerve is stimulated it
produces a wave of
depolarization i.e. nerve
impulse. This shows that it
has the property of
excitability.

Conductivity
It

is the ability of nerve to transmit

impulses from one point to the
other.
Nerve impulse conduction is active
& self propagating process.
The impulse moves at a constant
amplitude & velocity.

All or None Law

Once stimulus of threshold intensity is
reached, a full fledged AP is produced.
Further increase in the intensity of a
stimulus produce no increment or further
change in the AP as long as other
conditions remains constant.
AP fails to occur if the stimulus is of sub
threshold in magnitude, and it occurs with
constant amplitude and form regardless of
the strength of the stimulus if the stimulus
is at or above the threshold intensity. This
is called All Or NONE LAW

All or None Law

Once

the action potential has

started at any point on the
membrane depolarization process
will travels over the entire
membrane if the conditions are
right or it might not travel at all if
conditions are not right.

Refractory period
Refractory

Period
Absolute Refractory Period
Relative Refractory Period

Strength duration Curve

The relationship
between intensity
of stimulus
(voltage) & the
duration of
stimulus (time) is
called strengthduration curve.

Strength duration Curve

Two factors are important
Voltage
Duration
By varying these two factors and
plotting the results a curve is
obtained which is called strength
duration curve.

RHEOBASE
It the minimum voltage or current which when
applied for an adequately prolonged time will
be able to reach threshold and will give rise to
action potential.
UTILIZATION TIME
The minimum time required for current equal
to the rheobase to induce action potential.

CHRONAXIE
It

is the minimum time for which a

stimulus equal to twice the rheobase
(2xR) value has to be applied in order to
get action potential

Physiological Importance
Tissues which are more excitable
will have shorter CHRONAXIE.
Nerve fibers have shorter chronaxie
than muscles. Nerve fibers are more
excitable.
When injury to a motor nerve
chronaxie is increased

Objectives

At the end of lecture 1st yr MBBS student

must be able to:
Classify nerve fibers
Define compound action potential
Explain the Significance of compound
action potential
Explain recording of action potential

Explain Graded potential

Classification of Nerve
Fibers
Type A fibers (myelinated)
Alpha
Beta
Gamma
Delta
Type B fibers (myelinated)
Type C fibers (unmyelinated)

Compound Action
Potential

Multi-peaked action
potential recorded
from a mixed nerve
is a compound
action potential

It is due to different
type of fibers which
are present in a
mixed nerve.

Compound Action
Potential

It has a unique shape

Action potential from

the fastest conducting
fiber is the first to be
recorded followed by
the slower ones.

Compound Action
Potential
Nerve fiber with the largest
dia shows following
features.
Greater conduction
velocity.
Greater magnitude of
action potential.
Shorter duration of spike
potential.
Shorter refractory period.

Advantage of Compound
action Potential
On

the basis of compound

action potential we can
classify nerve fibers into
A,B,C types.

CLASSIFICATION
OF NERVE
FIBERS

Classification of Nerve
Fibers
Type A fibers (myelinated)
Alpha
Beta
Gamma
Delta
Type B fibers (myelinated)
Type C fibers (unmyelinated)

Classification of Nerve Fibers

Function

Fiber
Diameter
(m)

Conduction
Velocity
(m/s)

Proprioception;
somatic motor

12-20

70-120

Touch, pressure

5-12

30-70

Motor to muscle
spindles

3-6

15-30

Pain, cold, touch

2-5

12-30

Preganglionic
autonomic nerves

<3

3-15

Spike
Duration
(milli-sec)

Absolute
Refractory
Period
(milli-sec)

0.4-0.5

0.4-1

1.2

1.2

Classification of Nerve Fibers

Function

Dorsal root

Pain,
temperature

Sympathetic Postganglioni
c sympathetic

Fiber
Diameter
(m)

Conducti Spike
Absolute
on
Duration Refractory
Velocity
(milliPeriod
(m/s)
sec)
(milli-sec)

0.4-1.2

0.5-2

0.3-1.3

0.7-2.3

Role of K & Na Ions

Hypokalemia
- Hyperpolarization
Hyperkalemia
Depolarization
Hypocalcemia
Increase excitability
Hypercalcemia Decrease
excitability
(Membrane Stabilizer)

Recording of Action
Potential

Cathode Ray
Oscilloscope

Mono-Phasic AP

Microelectrode is inserted
inside of the fiber & the
other electrode is placed
outside.

GRADED
POTENTIAL /
LOCAL POTENTIAL

Graded Potential / Local

Potential
When a sub-threshold
stimulus is given there is no
generation of AP. But it
produces a local change in
the membrane potential
which is called GP/LP.

Graded Potential / Local

Potential
This

change is not propagated but is

observed at a very short distance from
the point of stimulus.
When Local depolarization reaches a
threshold level an explosive change in
the membrane potential occurs which is
called Action Potential or Nerve
Impulse.

Objectives
At the end of lecture 1st yr
MBBS student should be able to
Differentiate between graded
potential and action potential
Classify Nerve fibers

Graded Potential

Action Potential

Threshold

No threshold level is required,

response depends upon
strength of stimulus

Has threshold level

Amplitude

Varies with strength of stimuli

Fixed

Refractory
Period

No R.P

Has R.P

All or none
Law

Doesnt obey all & none law,

Response is graded

Obeys All & None Law

Duration

Prolonged in duration

Short duration

Self
Propagation

No self Propagation.
Decremental in character.
Decrease with distance.

Self Propagated

Nature

Excitatory or
inhibitory/hyperpolarization

Depolarization with
overshoot potential

Sites

Synapse, receptors, motor end

plates

Nerve, muscle

Classification on the basis of

susceptibility
Type

A fibers (myelinated)
Sensitive to pressure
Type B fibers (myelinated)
Sensitive to hypoxia
Type C fibers (unmyelinated)
Sensitive to local anesthetics

Objectives

At the end of the lecture MBBS student should

be able to:
Explain the effect of cutting the mixed nerve.
Explain the disorder of myelin sheath i.e.
multiple sclerosis
Discuss the causes and pathophysiology of
disease
Elaborate the sign and symptoms of disease
Explain how to diagnose and treat the
disease

Conduction Velocity
of Nerve Fibers
The

conduction velocity of nerve

fibers varies from 0.5 m/sec in
very small unmyelinated fibers
to as great as 120 m/sec in large
myelinated fibers.

Conduction velocity

If the duration of the latent period (T) and the

distance (S) between the electrodes are known, the
conduction velocity in the axon can be calculated.
For example, if the distance between the stimulating
electrode and the recording electrode is 4 cm. If the
latent period is 2 ms
S=VT
V=S
T
Conduction Velocity = 4 cm/2 ms, or 20 m/sec.

Distance is 4.5 cm
Latent period is 1.5ms
Conduction velocity ?
S=V/T
V=S/T

Effects of Cutting Mixed

Nerve Trunk

Loss of Motor Activity

Skeletal muscles get paralyzed & stops
showing reflex activity.
Loss of Muscles tone & loss of their mass.
Erbs reaction of degeneration.
Altered response of muscle to electric
stimulation seen after loss of their motor
supply
Loss of Sensations
Over the area supplied by the Nerve

Loss of Autonomic Nerve Activity

Loss of vasoconstrictor
tone/vasomotor tone resulting in
erythema of the skin, later on the
area become blue and cold.
Loss of Trophic action
Loss of growth promoting function
of nerve.
Taste buds

Mixed Nerve Fibers

Direction of propagation of action potential.

Motor fibers
Sensory fibers
Conduction Velocity of impulses
Myelinated (more velocity due to
myelination)
Diameter (more is the diameter more is the
conduction velocity)
Degree of Excitability
Differs with type of fibers

Clinical importance

Damage to nerves can be caused by

physical injury or swelling
carpal tunnel syndrome
Autoimmune diseases e.g.
Guillain-Barr syndrome
Infection e.g. neuritis
Nerve damage accompanied by pain,
numbness, weakness, or paralysis.

Patients may feel these symptoms in areas far from

the actual site of damage, a phenomenon called
referred pain .

Diagnosis
Physical examination
Testing of reflexes
Walking and other directed movements
Muscle weakness, proprioception , and the sense of
touch.
Tests
Nerve conduction study and Electromyography

Disorder of
Myelin Sheath

Multiple
Sclerosis

Multiple Sclerosis

Age 20-50yrs
Sex : more common in Females
Inflammatory and neuro- degenerative
disease

CAUSES

Causes
Genetics
Environmental

factors
such as viruses

Genetics

Environmental Factors
Viruses

Early exposure to viruses such as Epstein-B virus and

those that cause measles, herpes, chicken pox or

Patho-physiology
Antibodies and WBC attack myelin sheath
and cause inflammation and injury to the
myelin sheath & the nerves.
Gradual destruction of Myelin sheath around
axons of the brain & spinal cord.
Leakage of K+ through voltage-gated
channels results in hyper-polarization and
failure of transmission of nerve impulse.
impulse

Types
Transient

episodes appear

suddenly
Progressive form of the
disease

Main Sign &

Symptoms
Muscle

weakness

Fatigue
Diminished

coordination
Slurred speech
Blurred or hazy vision
Bladder & bowl dysfunction
Sensory disturbances

DIAGNOSIS

Diagnosis

Diagnosis
History & Physical Examination

TESTS
1. Nerve conduction tests
detect slow conduction in motor and
sensory
pathways
2. CSF analysis
oligoclonal bands indicative of an abnormal
immune reaction against myelin
3. Magnetic resonance imaging (MRI)
multiple scarred (sclerotic) areas in the brain.

Treatment
No

cure for MS
Immunosuppressant drugs like interferon
suppress the immune response
& reduce the severity and slow
the progression of the disease.

Treatment

GUILLAIN-BARRE
SYNDROME

Objectives

At the end of lecture 1stb yr MBBS

student should be able to:
Discuss causes, features,
pathophysiology, diagnosis and
treatment of GB syndrome

Guillain-Barre Syndrome
Auto immune disease
It is polyneuropathy
When the body's defense (immune)
system mistakenly attacks part of the
PNS.
This leads to nerve inflammation &
demyelination of the peripheral
nerves.

Sign & Symptoms

Gradual weakness and marked
slowing of the response.
Muscle weakness or (paralysis) affects
both sides of the body. In most cases,
the muscle weakness starts in the
legs and then spreads to the arms.
This is called ascending paralysis.
Breathing difficulty etc.

GB Syndrome

Diagnosis

History
Physical Examination
Nerve conduction test
Cerebrospinal fluid
Electromyography (EMG) tests the electrical
activity in muscles
Pulmonary function tests

T/M

High-dose immunoglobulin therapy

Objectives

At the end of lecture 1st yr MBBS

student should be able to:
Discuss causes of nerve injury,
degenerative and regenerative
changes after nerve injury.

DEGENERATION &
REGENERATION OF
NERVE FIBER

Degeneration of Nerve
Fiber

CAUSES

Trauma
Crushing
Section
Toxic

substance
Interference with blood
supply

Degenerative changes
depend upon the extent of
injury
In

First-Degree injuries there is no

true regeneration or degeneration.
In Second-Degree injury there is
little histological change proximal
to site of injury and distal to it there
is Wallerian degeneration.

 Impulses

conducted for 3
days after injury, later on it
decreases. After 5 days no
conduction of nerve impulse.

Degenerative changes
take place at three
levels
Cell

body
Proximal stump
Distal stump

Changes in Cell Body

Cell body swells up.

Nucleus pushed to one side.
Mitochondria, RER, Golgi app, lysosomes &
neurofibrils undergo structural changes and
degrades.
Chromatolysis of Nissle granules.
If severe injury nucleus is expelled out then
no regeneration takes place.

Changes in Proximal
stump
Degeneration process also
extends one or two nodes
upwards. Soon followed by
regeneration

Changes in Distal Stump/

Wallerian Degeneration
Degenerative

changes
in the distal segment
were observed by A H
Waller hence given the
name Wallerian
Degeneration.

Changes in Distal Stump/

Wallerian Degeneration
Changes begins to occur in 24-48 hrs &
are completed in 3 wks.
Swelling of the AXON
Axoplasm & axolemma become tortuous
and get fragmented in 1-2 days.
Swelling of myelin sheath.
Myelin sheaths separate from the axons
at the Schmidt-Lanterman incisures first
and then rapidly disintegrate and
shorten to form bead-like structures.

Schmidt-Lanterman
clefts/Incisures

Small amounts of Schwann cell

cytoplasm not displaced to the
periphery during formation of
the myelin.
They subdivide the myelinated
axon into irregular portions.
Oblique clefts may be seen in
the medullary sheath,
subdividing it into irregular
portions, which are termed
Schmidt-Lanterman clefts

Myelin sheath breaks into oily droplets.

Lecithin molecules present in the myelin
sheath break into
Fatty acid
Glycerol
Phosphoric acid
Choline
Schawann cells & macrophages increase
in number at site of injury in about 1 wk.
They release hydrolytic enzymes which
help in the destruction of myelin.

 In

the end only Endoneurium

persist with underlying
Neurilemma of the nerve
fiber that does not degenerate
and remains as a hollow
tube/endoneurial tubes.

Prerequisites for Nerve

Fiber Regeneration:

The gap between the cut ends should not

exceed 3mm.
Neurilemma should be present. As
Neurilemma is absent in CNS, so regeneration
does not occur in nerve fibers of CNS.
Nucleus should be intact.
The two cut ends should remain in the same
line.

Regeneration
Cell

Body
Distal stump

Regeneration
Within 96 hours of the injury,
the proximal end of the nerve
fiber sends out sprouts / fibrils
upto 50 to 100 in number
towards the endoneurial tubes.
The fibrils move towards the
distal cut end of the nerve fiber
and some of the fibrils enter the
endoneurial tube of distal end
and form axis cylinder

 Rapid

proliferation of schawann cells

occur which line up in the
endoneurial tube and guide the
fibrils into the tube
Schwann cells secrete growth
factors that attract the growing axon
If one
of the sprout / outgrowths
o
enters the endoneurial tube it grows
into it and advances about 1-4 mm
per day, eventually reach the target
tissue & forms a new axon.

 In

about three months time after

the injury, axis cylinder is fully
established inside the
neurilemmal tube
Schwann cells will spin around
the fiber and form myelin sheath.
Axoplasm flows into distal cut
end.

In the nerve cell body, series of

events takes place. First, the Nissl
granules appear followed by Golgi
apparatus. The cell loses all
excessive fluid and nucleus occupies
the central position. Anatomical
regeneration although occurs in the
nerve, however, functional recovery
occurs after a long time.

Regeneration
If distance between cut ends is more than
3mm then tumor like swelling is formed
called Neuroma
No regeneration in optic nerve and CNS
No endoneurial tubes so the regenerating
axon cannot be guided
No schawan cells instead
oligodendrocytes are present

SYNAPSE

Objectives
At the end of lecture 1st yr MBBS
student should be able to:
Define synapse
Classify synapse
Discuss chemical and electrical
synapse

Synapse
It

is a functional
connection between a
neuron and another
neuron or effecter cell.

 Impulses

are transmitted from

one cell to another cell at
synapse.
It allows a neuron to pass an
electrical or chemical signal to
another neuron.

Synapse
Neurons are linked to one another to form
conducting pathways. These links or
interneuronal junctions are called
SYNAPSE.
It is a junction where axon or some other
part of the neuron terminates on the
soma, dendrite or axon of other neuron .
First incoming neuron is presynaptic
neuron & second neuron to which activity
is transmitted is postsynaptic neuron.

Anatomical Classification of
Synapse
Axo-somatic
Axo-dendritic
Axo-axonic
Somato-dendritic
Somato-somatic
Dendro-dendritic

Classification of Synapse on
Geometric Basis
Simple synapse
Single pre-synaptic
component in contact
with one post-synaptic
structures.
Complex synapse
One pre-synaptic
component comes in
contact with two postsynaptic structures.

Serial synapse
3 structures are
arranged serially, activity
from one conducted to
second and then to third.
Reciprocal synapse
Activity passes from one
cell to second cell and
from the second cell
back to the first one.
Neuron will have
presynaptic & postsynaptic functions.

Functional
classification of
synapse
Electrical Synapse
Chemical Synapse
Mixed synapse

Electrical
Synapse

Electrical Synapse
The membranes of the pre- and
postsynaptic cells are joined by GAP
junctions at electric synapses.
The two membranes are very close to
each other (synaptic cleft 2nm). They
are connected to each other through
GAP junctions.
There is rapid transmission of electrical
signals between cells due to gap
junctions.

 Gap

junctions are permeable to ions,

have low electrical resistance.
These gap junctions are present where
rapid transmission is required or extreme
degrees of synchronization is required.
GAP junctions are present in:
Smooth (intestines) and cardiac
muscles, brain, and glial cells.

Electrical Synapse

Gap junctions:
Adjacent cells
electrically joined
through a channel
formed by Connexin
proteins, arranged in
a hexagonal pattern
forming gap
junctions.
These channels link
the cytoplasm of 2
cells.

Chemical
Synapses

Chemical Synapses
Chemical

synapses are
specialized junctions through
which neurons send chemical
signals to each other and to nonneuronal cells such as those in
muscles or glands.

Chemical Synapse
Functional Anatomy of
Synapses
It is a classical synapse,
formed between axon

terminals & soma of the motor neurons.

Membrane of pre-synaptic neuron is separated
from the membrane of post-synaptic neuron by a
space which is called synaptic cleft (20nm).
A large number of small vesicles & mitochondria
are present in the pre-synaptic terminals.
Vesicles contain neurotransmitter which is
formed in the cell body by ER & packed in GA &
transported by axoplasmic flow to the terminal
knob.

Chemical Synaptic
Transmission

When an
action potential
travels along the
axon of a neuron and
reaches at synapse it
causes release of
neurotransmitter
which bind to
receptors in the
membrane of post
synaptic neuron

Events in Synaptic
Transmission

Nerve impulse comes along the nerve

terminals & reaches the presynaptic
membrane.
Depolarization of the presynaptic
membrane.
Opening of voltage gated Ca channels.
Ca moves in the membrane.
Binds to a protein in the cytoplasm
called calmodulin.

 Calmodulin

activates an enzyme
called protein kinase.
Protein kinase causes
phosphorylation of protein synapsin
in the membrane of synaptic vesicle.
Fusion of synaptic vesicles with the
plasma membrane.
Release of neuro-transmitter by
exocytosis.

Chemical Synapse
Amount of NTs
released
depends upon
frequency of AP
Post-synaptic
membrane
contains
receptors for
binding the NTs

Synaptic Transmission

Synaptic Transmission

NT (ligand) binds to receptors in

postsynaptic membrane & brings about
changes in membrane permeability.
ligand gated channels open.
Depending on the type of changes produced
in the membrane potential the post-synaptic
membrane is stimulated or inhibited.

(continued)

EPSP: depolarization.
IPSP: hyperpolarization.

Neurotransmitter inactivated to end

transmission.

Questions
Mechanism

of transmission
of nerve impulse across
chemical synapse?
Synaptic transmission?

Objectives

At the end of lecture 1st yr MBBS student

should be able to
Discuss

the post-synaptic potential

Describe post-synaptic and pre-synaptic
inhibition
Define summation, enumerate the types of
summation
Explain the types of summation
Discuss the properties of synaptic transmission

Post-synaptic potential
Depending

upon the
neurotransmitter involved,
chemical transmission results in
either an EPSP or IPSP .
Post-synaptic potential is of two
types.
EPSP
IPSP

EPSP (Excitatory Postsynaptic

Potential)

When a single stimulus is applied to a nerve ,

it produces a partial depolarization of the
post-synaptic neuron & does not lead to the
formation of a propagated action potential.
An excitatory neurotransmitter produces
EPSP.
NT increases Na & K permeability, Na influx
takes place.
EPSP brings the RMP to the threshold level.
When it reaches the firing level action
potential is produced.

EPSP (excitatory postsynaptic

potential)

It resembles end plate potential.

Shows a graded response.
It does not obey all & none law.
Does not propagate.
It has No RP
The EPSP due to partial
depolarization of one synaptic
knob is small but the partial
depolarization produced by each
of the synaptic knobs summate
& produces action potential.

Advantage of EPSP

EPSP

Action
Potential

Magnitude

low

high

Refractory
Period

No R.P

Has R.P

All or none
Law

Response is graded,
Obeys All & None
doesnt obey all & none law Law

Duration

Prolonged in duration

Self
No self Propagation.
Propagation Decremental in character.
Decrease with distance.

Short duration
Self Propagated

IPSP (Inhibitory Postsynaptic

Potential)

It is produced when post synaptic

neuron is inhibited. HOW?
Inhibitory neurotransmitter is
released GABA, Glycine.
Permeability for K+ & Cl- is
increased.
Inside becomes more negative
i.e. Hyperpolarization occurs.
There is Hyperpolarization of the
post-synaptic membrane.
This results in inhibition of the
post synaptic neuron. This is
called IPSP.

Pre-synaptic inhibition

Presynaptic inhibition
Pre-synaptic knob (B) has
additional synapse with
nerve terminal (A) & from
this additional synapse
there is release of NT
which will inhibit the presynaptic knob (B).
The amount of an
excitatory NT released at
the end of an axon (B) is
decreased by the effects of
a inhibitory NT from
neuron (A).

Post-synaptic inhibition
When the inhibitory neurotransmitter
is released there is inhibition of post
synaptic membrane and the Post
synaptic membrane is hyperpolarized
Post-synaptic inhibition when
potential in the post synaptic neuron
changes from
-70 to -80mv or -90mv.

Summation

Summation
When

2 or more subthreshold stimuli combine

to cause excitation this
phenomenon is called
Summation.

Summation
There are 1000 synapse on a single motor
neuron.
Neuron receives multiple inputs from
excitatory & inhibitory neurons.
A single impulse cannot excite motor
neuron. In order to excite motor neuron
there must be summation of the effects of
stimuli.
Generation of action potential depends
upon summation of these multiple inputs.

Types of Summation

Types
Temporal

Summation
Spatial
Summation

Temporal Summation
When 2 subthreshold stimuli are
applied one after the
other, the effects are
added & excitation
occurs.
2nd stimulus falls
when the effect of
first stimulus is still
there.

Spatial Summation

When 2 or more subthreshold stimuli are

applied simultaneously.
These stimuli summate
to produce depolarization
& cause excitation.
Impulses are coming
along number of synaptic
knobs these effects are
added & results in
SPATIAL summation

Properties of
Synaptic
Transmission

Properties of Synaptic
Transmission
Uni-Directional Conduction
Synaptic Delay
Summation
Fatigue of Synaptic Transmission
Dales law
Effected by Hypoxia, Drugs,
Anesthetics, Acidosis, Alkalosis &
Ischemia.

Uni-Directional
Conduction
Impulses are conducted through the

synapse from pre-synaptic neuron to the

post-synaptic neuron in only one direction
this is called ORTHODROMIC
conduction.
Motor nerves ----------- muscles
Sensory nerves -------- CNS.
Reciprocal synapse are exception to this
rule

Synaptic Delay
It

is due to the time taken in the

events during impulse transmission
from pre-synaptic neuron to the
post-synaptic neuron.
In each synapse delay is about 0.5
milli sec.

Summation
Temporal

summation
Spatial summation

Fatigue of Synaptic
Transmission

When impulses are conducted rapidly &

repeatedly one after the other, there is
fatigue of synapse.
Causes
Exhaustion of neurotransmitter
Progressive inactivation of receptors at
post-synaptic membrane.
Advantage:
It is protective in a nature. It leads to
termination of epileptic fits

Dales law

At one synapse only one

type of neurotransmitter is
released it may be
excitatory or inhibitory

Effects of Hypoxia, Drugs,

Anesthetics, Acidosis, Alkalosis &
Ischemia.
Hypoxia
Depresses synaptic transmission
Anesthetics
Depresses excitability
Acidosis
Depresses excitability
Drugs
Caffeine, Theophyllin increases excitability
Alkalosis
Increases excitability

Toxins which can affect

Synaptic Transmission

Tetanus toxin
Botulinum toxin
These are bacterial products that cause
paralysis by preventing
neurotransmission.

These neurotoxins function as proteases

(protein-digesting enzymes), digest the
fusion complex and inhibiting the
exocytosis and release of neurotransmitter.

Clinical Aspects

Botulinum toxin prevents the release

of Ach at the NMJ, causing flaccid
paralysis.

Tetanus toxin blocks inhibitory

synapse causing inhibition of release of
inhibitory NT leading to continuous
excitation and contraction which leads
to spastic paralysis.

Botulinum (BOTOX) injections are

helpful in muscle hyperactivity states.
Injection

in Lower Esophageal
Sphincter is given to relieve
ACHALASIA

Injection

given in facial muscles to

remove Wrinkles

BIPHASIC ACTION
POTENTIAL

Biphasic Action Potential

Both

recording electrodes are on

the outside of the nerve
membrane.
It is conventional to connect the
leads in such a way that when the
first electrode becomes negative
relative to the second, an upward
deflection is recorded.

Biphasic Action Potential

As the action potential moves farther

down the nerve fiber it will come to the
point when the membrane beneath the
first electrode becomes re-polarized
whereas the second electrode is now
negative the oscilloscope will record in
the opposite direction.

 Therefore,

the record shows

an upward deflection
followed by an isoelectric
interval and then a
downward deflection.

Alzheimers disease

The most common cause

of senile dementia,
produces progressive
mental deterioration.
Loss of cholinergic
neurons.
Treatments includes the
use of
Anticholinesterase to
increase Acetyl-choline
transmission in the
brain.

Accomodation

Nerve has the property of accomodation

Nerve responds only to rapidly rising currents.
If the intensity of the stimulus is increased too
slowly the threshold increases slowly (nerve
accomodates to the passage of current).
It is better to apply the stimulus which rise
extremely rapidly.

Neurotransmitters

Acetyl-choline
Epinephrine
Norepinephrine
Dopamine
Serotonin
Glycine
GABA
Substance P

Acetylcholine (ACh) as NT

ACh is both an excitatory and

inhibitory NT, depending on organ
involved.
Excitatory in skeletal muscles when
bind to nicotinic receptors.
Inhibitory in cardiac muscle when
binds to Muscrinic receptors

Acetyl-Choline Receptors

Nicotinic ACh receptors:

Skeletal muscle
Autonomic ganglia

Muscarinic ACh receptors:

Smooth muscle
Cardiac muscle
In cells of particular glands

Ligand-Operated ACh
Channels/
Nicotinic Ach receptors

Schmidt-Lanterman
clefts/Incisures

Small amounts of Schwann cell

cytoplasm not displaced to the
periphery during formation of
the myelin.
They subdivide the myelinated
axon into irregular portions.
Oblique clefts may be seen in
the medullary sheath,
subdividing it into irregular
portions, which are termed
Schmidt-Lanterman
incisures

Ligand-Operated ACh
Channels/
Nicotinic
Ach
receptors
Ion channel run through
receptor.
Receptor has 5

Channel opens when

both sites bind to ACh.

polypeptide subunits
that enclose ion channel.
2 subunits contain ACh
binding sites.
Permits diffusion of Na+
into and K+ out of
postsynaptic cell.

Inward flow of Na+

dominates.

Produces EPSPs.

G Protein-Operated ACh
Channel/ Muscrinic ACh
Receptors

G Protein-Operated ACh
Channel/ Muscrinic ACh
receptors
Only 1 subunit.
Ion channels are
separate proteins
located away from
the receptors.
Binding of ACh
activates alpha Gprotein subunit.
Alpha subunit
dissociates.
Alpha subunit or the
beta-gamma
complex diffuses
through membrane
until it binds to ion
channel, opening it.

Alzheimers disease

The most common cause

of senile dementia,
produces progressive
mental deterioration.
Loss of cholinergic
neurons.
Treatments includes the
use of Anticholinesterase
to increase Acetyl-choline
transmission in the brain.

Myasthenia Gravis

Muscle weakness in the disease myasthenia

gravis is due to the fact that ACh receptors are
blocked and destroyed by antibodies secreted by
the immune system of the affected person.
Paralysis in people who eat shellfish poisoned
with saxitoxin, or pufferfish containing
tetrodotoxin, results from the blockage of Na+
channels.

ACh in CNS

Cholinergic neurons:

Use ACh as NT.

Axon bouton synapses with dendrites or cell
body of another neuron.

First VG channels are located at axon

hillock.
EPSPs spread by cable properties to initial
segment of axon.
Gradations in strength of EPSPs above
threshold determine frequency of APs
produced at axon hillock.

ACh in PNS

Somatic motor neurons synapse

with skeletal muscle fibers.

Release ACh from boutons.

Produces end-plate potential (EPSPs).

Depolarization opens VG channels

adjacent to end plate.

Norepinephrine (NE) as NT

NT in both PNS and CNS.

PNS:

Smooth muscles, cardiac muscle and

glands.

Increase in blood pressure, constriction of

arteries.

CNS:

General behavior.

Monoamines as NT

Monoamine NTs:

Epinephrine.
Norepinephrine.
Serotonin.
Dopamine.

Inhibition of Monoamines
as NT

Reuptake of
monoamines into
presynaptic
membrane.

Enzymatic
degradation of
monoamines in
presynaptic
membrane by MAO.

Enzymatic
degradation of
catecholamines in
postsynaptic
membrane by COMT.

Mechanism of Action

Monoamine NT do not
directly open ion channels.
Act through second
messenger, such as cAMP.
Binding of norepinephrine
stimulates dissociation of
G-protein alpha subunit.
Alpha subunit binds to
adenylate cyclase,
converting ATP to cAMP.
cAMP activates protein
kinase, phosphorylating
other proteins.
Open ion channels.

Serotonin as NT

NT (derived from L-tryptophan) for neurons

with cell bodies in raphe nuclei.
Regulation of mood, behavior, appetite, and
cerebral circulation.
SSRIs (serotonin-specific reuptake inhibitors):

Inhibit reuptake and destruction of serotonin,

prolonging the action of NT.
Used as antidepressant.

Reduces appetite, treatment for anxiety, treatment

for migraine headaches.

Dopamine an NT

NT for neurons with cell bodies in midbrain.

Axons project into:

Nigrostriatal dopamine system:

Nuerons in substantia nigra send fibers to corpus straitum.

Initiation of skeletal muscle movement.
Parkinsons disease: degeneration of neurons in substantia
nigra.

Mesolimbic dopamine system:

Neurons originate in midbrain, send axons to limbic system.

Involved in behavior and reward.
Addictive drugs:

Promote activity in nucleus accumbens.

Norepinephrine (NE) as NT

NT in both PNS and CNS.

PNS:

Smooth muscles, cardiac muscle and

glands.

Increase in blood pressure, constriction of

arteries.

CNS:

General behavior.

Amino Acids as NT

Glutamic acid and aspartic acid:

Major excitatory NTs in CNS.
Glutamic acid:
NMDA receptor involved in memory storage.
Glycine:
Inhibitory, produces IPSPs.
Opening of Cl- channels in postsynaptic membrane.

Hyperpolarization.

Helps control skeletal movements.

GABA (gamma-aminobutyric acid):
Most prevalent NT in brain.
Inhibitory, produces IPSPs.

Hyperpolarizes postsynaptic membrane.

Motor functions in cerebellum.

Polypeptides as NT

CCK:

Substance P:

Promote satiety following meals.

Major NT in sensations of pain.

Synaptic plasticity
(neuromodulating effects):

Neurons can release classical NT or the

polypeptide NT.

Polypeptides as NT

Endogenous opiods:

Brain produces its own analgesic endogenous morphine-like

compounds, blocking the release of substance P.

Beta-endorphin, enkephalins, dynorphin.

Neuropeptide Y:
Most abundant neuropeptide in brain.
Inhibits glutamate in hippocampus.
Powerful stimulator of appetite.
NO:

Exerts its effects by stimulation of cGMP.

Macrophages release NO to helps kill bacteria.

Involved in memory and learning.
Smooth muscle relaxation.

Endogenous Cannabinoids,
Carbon Monoxide

Endocannabinoids:

Bind to the same receptor as THC.

Act as analgesics.
Function as retrograde NT.

Carbon monoxide:

Stimulate production of cGMP within neurons.

Promotes odor adaptation in olfactory
neurons.
May be involved in neuroendocrine regulation
in hypothalamus.

EPSP

No threshold.
Decreases resting
membrane
potential.

Closer to threshold.

Graded in
magnitude.
Have no refractory
period.
Can summate.

Synaptic Integration

EPSPs can summate,

producing AP.

Spatial summation:

Numerous boutons
converge on a single
postsynaptic neuron
(distance).

Temporal summation:

Successive waves of
neurotransmitter
release (time).

Long-Term Potentiation

May favor transmission along frequently

used neural pathways.
Neuron is stimulated at high frequency,
enhancing excitability of synapse.

Improves efficacy of synaptic transmission.

Neural pathways in hippocampus use

glutamate, which activates NMDA
receptors.

Involved in memory and learning.

Synaptic Inhibition

Presynaptic inhibition:

Amount of excitatory NT
released is decreased by
effects of second neuron,
whose axon makes
synapses with first
neurons axon.

Postsynaptic inhibition
(IPSPs):

No threshold.
Hyperpolarize
postsynaptic membrane.
Increase membrane
potential.
Can summate.
No refractory period.

MCQS Nerve Physiology

Chapter 7

1. The supporting cells that form myelin sheaths in the peripheral nervous
system are
a. oligodendrocytes.
b. satellite cells.
c. Schwann cells.
d. astrocytes.
e. microglia.
2. A collection of neuron cell bodies located outside the CNS is called
a. a tract.
b. a nerve.
c. a nucleus.
d. a ganglion.
3. Which of these neurons are pseudounipolar?
a. sensory neurons
b. somatic motor neurons
c. neurons in the retina
d. autonomic motor neurons

4. Depolarization of an axon is produced by

a. inward diffusion of Na+.
b. active extrusion of K+.
c. outward diffusion of K+.
d. inward active transport of Na+.

5. Repolarization of an axon during an

action potential is produced by
a. inward diffusion of Na+.
b. active extrusion of K+.
c. outward diffusion of K+.
d. inward active transport of Na+.

6. As the strength of a depolarizing stimulus to an

axon is increased,
a. the amplitude of action potentials increases.
b. the duration of action potential increases.
c. the speed with which action potentials are
conducted increases.
d. the frequency with which action potentials are
produced increases.
7. The conduction of action potentials in
myelinated nerve fiber is
a. saltatory.
b. without decrement.
c. faster than in an unmyelinated fiber.
d. all of the these.

8. Which of these is not a characteristic of synaptic

potentials?
a. They are all or none in amplitude.
b. They decrease in amplitude with distance.
c. They are produced in dendrites and cell bodies.
d. They are graded in amplitude.
e. They are produced by chemically regulated
gates.
9. Which of these is not a characteristic of action
potentials?
a. They are produced by voltage regulated gates.
b. They are conducted without decrement.
c. Na+ and K+ gates open at the same time.
d. The membrane potential reverses polarity during
depolarization.

10. A drug that inactivates acetylcholinesterase

a. inhibits the release of ACh from presynaptic
endings.
b. inhibits the attachment of ACh to its receptor
protein.
c. increases the ability of ACh to stimulate muscle
contraction.
d. does all of the these.
11. Postsynaptic inhibition is produced by
a. depolarization of the postsynaptic membrane.
b. hyperpolarization of the postsynaptic membrane.
c. axoaxonic synapses.
d. long-term potentiation.

12. Hyperpolarization of the postsynaptic

membrane in response to glycine or GABA is
produced by the opening of
a. Na+ channels.
b. K+ channels.
c. Ca2+ channels.
d. Cl channels.
13. The absolute refractory period of a neuron
a. Is due to the high negative polarity of the
inside of
the neuron.
b. occurs only during the repolarization phase.
c. occurs only during the depolarization phase.
d. occurs during depolarization and the first part
of the repolarization phase.

14. Which of these statements about catecholamines is false?

a. They include norepinephrine, epinephrine, and dopamine.
b. Their effects are increased by action of the enzyme
catechol O methyltransferase.
c. They are inactivated by monoamine oxidase.
d. They are inactivated by reuptake into the presynaptic axon.
e. They may stimulate the production of cyclic AMP in the
postsynaptic axon.
15. The summation of EPSPs from numerous presynaptic
nerve fibers converging onto one postsynaptic neuron is
called
a. spatial summation.
b. long-term potentiation.
c. temporal summation.
d. synaptic plasticity.

16. Which of these statements about Ach receptors is

false?
a. Skeletal muscles contain nicotinic ACh receptors.
b. The heart contains muscarinic ACh receptors.
c. G-proteins are needed to open ion channels for
nicotinic receptors.
d. Stimulation of nicotinic receptors results in the
production
of EPSPs.
17. Hyperpolarization is caused by all of these
neurotransmitters except:
a. glutamic acid in the CNS.
b. ACh in the heart.
c. glycine in the spinal cord.
d. GABA in the brain.

Key Nerve

1. c
2. d
3. a
10. c
11. b
12. d

4. a
5. c
6. d
13. d
14. b
15. a

7. d
8. a
9. c
16. c
17. a