Nerve and Muscle Mbbs First Year Physiology .pdf

MBBS Physiology

1. Nerve & Muscle
Dr. Sauda Usmani
Assistant Professor
MBBS (KEMU)
FCPS Physiology (CPSP)

3. By the end of this lecture
you should be able to:
MS-P
004
Describe the Physiological anatomy of
Neurons

Enlist & give functions of Neuroglial cells
Explain process of myelination in CNS &
PNS

Discuss the axonal transport
1

4. Nervous tissue
◼Nervous tissue consists of neurons and neuroglia
◼Neurons are building blocks of nervous system
◼Neuroglia: glia= glue
1.Microglia: these are phagocytes that remove tissue
debris after infection and injury
2.Macroglia:
Oligodandrocyte: form myelin sheath around
nerve fibers in CNS
Schwann cell: form myelin sheath in PNS
Astrocytes: Take part in generation of blood-brain
barrier. Produce substances that are tropic to neurons

5. ◼All substances ( many drugs and chemicals)
cannot pass Blood-Brain barrier
◼There is selective permeability of capillary
membrane in brain for appropriate
concentration of ions and neurotransmitters.
◼Small molecules, lipid soluble substances can
pass
◼Apical membrane of two adjacent cell surfaces
can fuse to form tight junctions
◼Glial cells continue to proliferate throughout life,
especially after stroke.

6. Neuron
◼In nervous system, more than 100 billion neurons
in human body
◼Consists of cell body SOMA containing nucleus
and cytoplasm (perikaryon).
◼Two types of processes:
1.Dendrites
2.Axons

7. AXON HILLOCK (site of generation of
nerve impulse)

8. Soma
◼Sizes are different
◼There is nucleus and cell organelles,
mitochondria, Golgi apparatus, neurofibrils,
endoplasmic reticulum and nissel body
◼No centrioles. Thus neurons can’t divide or
regenerate

9. Nissel body
◼Nissel body takes up basic dye (e.g. hematoxylin
and chromophill)
◼Nissel body is composed of RNA and Protein
◼Their no depends upon the physiological
condition of the neuron
◼Fatigue, toxins, damage or section of nerve fiber
results into breakdown of nissel bodies i.e.
chromatolysis

10. Function of nissel body
◼Protein synthesis
◼If nerve fiber regenerates after damage, nissel
body reappear

11. Dendrites
◼Dendrites are short and branching
◼In a neuron there may be no dendrites, or one or
more than one dendrite
◼Nissel granules are present

12. Axon
◼It is always one in neuron
◼Nerve fiber length may be long, i.e. few mm to more than
1 meter as in sciatic nerve
◼Thickness of nerve fiber axon varies (0.1 to 10 micrometer)
or even more
◼The terminal part of axon have multiple granules having
knob like ends called synaptic knobs, end feet or simply
nerve terminal
◼There are vesicles in nerve terminals and mitochondria
◼These vesicles contain neurotransmitter
◼Axon and axon hillock are devoid of Nissl granules

13. Myelin sheath
◼White shiny covering of nerve fiber
◼It is interrupted at regular intervals called nodes of Ranvier
◼Composed of multiple layers of cell membranes/Schwann
cells wrapped concentrically around nerve fiber to form
myelin sheath
◼Contains lipids, cholesterol, proteins
◼Schwann cell forms MS around nerve fiber in PNS
◼ In one internode one Schwann cell will form myelin
sheath
◼One nucleus of Schwann cell in one internode

14. Myelogenesis
◼Cell membrane of Schwann cell wraps around and rotated
concentrically around nerve fiber to form myelin sheath
◼Compacted and compressed by Protein Zero (Po) among adjacent
membranes
◼The outermost layer of myelin sheath is neurilemma. It is not
compressed and contains nucleus of Schwann cell
◼Myelin contains lipid substance sphingomyelin that is an excellent
electrical insulator
◼At node of Ranvier there is no myelin sheath but neurilemma is present
◼So nodes of Ranvier are highly permeable to ions
◼Where myelin sheath is present, there is no transmission of nerve
impulse

15. ◼Length of internode is variable between 0.1-10
mm
◼Thicker the nerve fiber, longer will be the
internode and greater will be velocity of
conduction
◼Schwann cells retain their ability to form myelin
sheath throughout life
◼If there is injury in PNS, regeneration of nerve
fibers in PNS
◼In CNS, oligodandrocytes are present. Once
these are formed, myelin sheath looses their
ability to form again
◼Myelin sheath formation around nerve fibers,
especially in CNS is completed in 2
nd
year of life

16. ◼One oligodandrocyte causes formation of myelin
sheath around 40 nerve fibers
◼No regeneration in CNS
◼Nerve fibers which are unmyellinated are highly
permeable to ions

18. Functions of myelin sheath
◼Prevent spread of action potential from one
nerve fiber to others as myelin sheath is insulator
◼Because of myelin sheath , nerve fiber has
greater velocity of conduction

◼Destruction of myelin sheath by antibodies
against it results in the disease Multiple Sclerosis

19. Which nerve fibers are
myellinated and which are
not?
◼Autonomic nerve fibers which are preganglionic
and somatic nerve fibers having diameter > 1
micrometer are myelinated
◼Autonomic nerve fibers which are postganglionic
and somatic nerve fibers having diameter < 1
micrometer are unmyelinated

20. Nervous system
physiologically divided into
2 types
◼Somatic NS: Skeletal muscles which are in our
control are supplied by somatic NS
◼Autonomic nervous system :
1.Sympathetic
2.Parasympathetic
Viscera not in our control (CVS, GIT) are
supplied by ANS

21. Axonal
transport/Axoplasmic
transport
◼“Transport of chemicals, vesicles and cell
organelles along the interior of axon”
◼Cytoplasm of axon is axoplasm
◼Functional integrity of nerve fiber depends on cell
body. Materials formed in cell body are
transported to synaptic knob terminals through
axoplasm
◼In axoplasm microtubules are present. Through
these transport of materials and substances
occurs

22. Two proteins involved in
Axoplasmic transport
◼Kinin or kinesin (anterograde/orthograde =cell
body to axon)
◼Dynein (retrograde=axon to cell body)
◼In synaptic knobs there are vesicles that store
neurotransmitter.
◼These vesicles are formed in the cell body

23. Draw on sketch book!!

25. Axonal transport involves 2
components
◼Fast component microtubules transport material and
structures i.e. vesicles and mitochondria
(400mm/day)
◼Slow component is because of protein mediated
cytoplasmic flow, transports enzymes (10 mm/day)
◼E.g.. Of anterograde transport: Herpes simplex &
varicella zoster virus from dorsal root ganglion to skin
◼E.g.. Of retrograde transport: Reuptake of
acetylcholine vesicles, polio virus, tetanus toxin (200
mm/day)

27. By the end of this lecture
you should be able to:

MS-P 011
Medical
Physiolog
y
integrate
with
Medicine
 
Enlist the types of nerve injury

Explain Wallerian degeneration.
Describe the process of regeneration of
nerve fiber.

Describe the causes, features &
pathophysiology of Multiple sclerosis, GB
syndrome.
 
2

28. Nerve Injury
◼The three most common mechanisms of injury
for peripheral nerves are stretch related,
lacerations, and compressions. Radiation,
electricity, injection, crush, cold injury, and
intra-neural and extra-neural pathologies
could also result in peripheral nerve injuries.
◼Stretch related: Due to the elastic nature of
peripheral nerves, stretch related injuries can
occur if a traction force is too strong for the
nerve’s elasticity. If the traction force exceeds
the nerves stretch abilities, a complete tear
could occur. However, it is more common that
the continuity of the nerve is retained during
this type of injury.

29. ◼Lacerations: Laceration injuries are the
second most common types of
peripheral nerve injuries. With this
mechanism of injury, a nerve is severed
partially or fully by some type of sharp
object. Most common lacerations are
from knives, broken glass, metal shards
etc. Due to the varying nature of damage
resulting from lacerations, we refer to
Seddon’s and Sunderland’s
classification systems which are
discussed below.

30. ◼Compressions: Compression nerve injuries
typically affect large-caliber nerves that
cross over bony structures or between rigid
surfaces. Acute compression (e.g. Saturday
Night Palsy) and chronic compression
injuries (e.g. carpal tunnel syndrome) are
the two main subcategories for
compression injuries. Compressive nerve
injuries can result in complete functional
loss of both motor and sensory function
even though the nerve fibers are still intact.
Two pathological mechanisms have been
thought to contribute to these types of
injuries: mechanical compression and
ischemia. Mechanical compression could
result in secondary ischemia issues which
can compromise nerve microcirculation

31. Seddon Classification

SeddonProcess
Sunderlan
NeurapraxiaThis type of nerve injury is usually secondary to
compression pathology. This is the mildest form of
peripheral nerve injury with minimal structural
damage. This allows for a complete and relatively
short recovery period.
In a neuropraxic injury, a focal segment of the
nerve is demyelinated at the site of injury with no
injury or disruption to the axon or its surroundings.
There is no Wallerian degeneration 
1
st

degree
AxonotmesisAn axonotmesis injury involves damage to the axon
and its myelin sheath. However, the endoneurium,
perineurium, and epineurium remain intact.
Although the internal structure is preserved, the
damage of the axons does lead to Wallerian
degeneration.
This type of nerve injury also results in a complete
recovery although it does take longer than a
neuropraxic injury.
2
nd
and
3
rd

degree
NeurotmesisA 3rd-degree neurotmesis injury is the disruption of
the axon and endoneurium. When this occurs the
perineurium and epineurium remain intact.
Disruption of the axon and perineurium is
considered a 4th-degree injury.
Complete disruption of the entire nerve trunk is
classified as a 5th-degree injury.
 
3
rd
, 4
th

and 5
th

degree

32. Wallerian degeneration
◼Waller, a scientist, first described these “sequence of
events that occur after nerve injury”
◼Nerve fiber is degenerated when it is
1. Sectioned or cut
2.crush injury of nerve fiber
3.injection of a toxic substance
4.interference with blood supply
5.or disease such as diabetes mellitus

33. Changes that occur
◼Within 24 hours of nerve injury changes start in the
nerve fiber
◼Changes in distal segment:
◼Axon swelling and broken into pieces. After few
days little debris is left behind in place of nerve
fiber
◼Myelin sheath becomes swollen and broken into
pieces. Oily droplets are left behind. At this stage
degenerating nerve fiber can be identified by
marchi staining

34. Wallerian degeneration and
regeneration

35. Marchi staining
◼Nerve fiber becomes black with this stain when
undergoing degeneration
◼Becomes +ve in 8-10 days of degeneration.
◼Endoneurium contains macrophages.
◼Schwann cells also contain hydrolytic enzymes
◼These hydrolytic enzymes from macrophages
and Schwann cells causes degeneration of axon
and myelin sheath

36. ◼Up to 3 days after nerve fiber section, the distal
segment continues to conduct nerve impulse.
◼Endoneural tube and Schwann cells are left
behind after nerve fiber degeneration in distal
segment
◼Changes in the proximal segment are limited to
the first internode from the cut segment

37. Changes in the cell body
◼Within 48 hrs. changes occur in the cell body
◼Swelling occurs. It becomes rounded
◼Nucleus becomes peripheral. In case of severe
injury nucleus may be expelled out, and in that
case there will not be regeneration if nucleus is
expelled out
◼There is chromatolysis “breakdown of nissel
bodies” or axonal reaction
◼Breakdown of Golgi, neurofibrils and
mitochondria

38. These changes depend
upon two factors
◼Severity of injury
◼Proximity of the section of nerve fiber to the cell body
◼If more severe injury, nucleus is expelled out
◼If section is close to cell body, more changes in cell
body
◼If there is injury to cell body then there is no
regeneration
◼If conditions are favorable there is nerve fiber
regeneration

39. Regeneration of nerve fiber
◼Process of regeneration starts about 3 weeks after
degeneration
◼If conditions are favorable only then it will start
and take 3 months for regeneration
◼From the cut end of distal segment: Schwann
cells divide to give thin elongated cells. These
grow in all directions but their useful growth will
be towards the cut end of the proximal segment
◼In this way the gap between the cut ends of two
segments is filled up by Schwann tissue

40. ◼Gap between cut ends up to 3mm can be easily
filled up by Schwann tissue
◼If gap is larger, the cut ends of the nerve fiber
can be stitched together to reduce gap
◼Fibroblasts lay down fibers to form a union scar
tissue
◼Axon from the cut end of the proximal segment
give rise to pseudopodia like fibrils. These fibrils
grow towards the cut end of distal segment, and
this growth is guided towards the distal segment
by Schwann cell growth
◼To start with, 50 -60 fibrils grow, but after
sometime only one of these continues to grow
into distal segment, others degenerate

42. ◼The fibril which enters the distal segment grows at
1 mm/day
◼The newly regenerated nerve fiber attain
diameter no more than 80% of normal fiber. So
functionality returns after regeneration but never
100%
◼Schwann cells form myelin sheath around
regenerated nerve and this takes up to 1year
◼Nerve fiber regeneration takes 3 months

43. When regeneration occurs,
changes also occur in cell
body
◼Nucleus becomes central
◼Nissel bodies, Golgi, neurofibrils and mitochondria
reappear
◼Trophic factors: Proteins known to affect the
growth of axons and maintenance of synaptic
connections. (astrocytes)
◼Nerve growth factor
◼Brain derived growth factors; neurotrophin 3,4
and 5, ciliary neurotrophic factor

45. By the end of this lecture
you should be able to:

MS-P 011
Medical
Physiology
integrate
with
Medicine
 
Enlist the types of nerve injury

Explain Wallerian degeneration.
Describe the process of regeneration of
nerve fiber.

Describe the causes, features &
pathophysiology of Multiple sclerosis, GB
syndrome.
 
3

46. Multiple Sclerosis (MS) &
Guillain–Barré (GB) Syndrome:
◼Normal conduction of action potentials relies on
the insulating properties of myelin. Thus, defects
in myelin cause neurologic conduction defects.
◼In Multiple Sclerosis, patchy destruction of
myelin occurs in the CNS. The loss of myelin
causes delayed or blocked conduction in the
demyelinated axons.
◼Myelin protein zero (P0) and a hydrophobic
protein PMP22 are components of the myelin
sheath in the peripheral nervous system.
Autoimmune reactions to these proteins cause
Guillain–Barré syndrome, a peripheral
demyelinating neuropathy.

47. Multiple Sclerosis (MS):
◼An autoimmune disease, affects over 3 million
people worldwide, usually striking between the ages
of 20 and 50
◼affecting women about twice as often as men.
◼The causes of MS: Genetic and environmental
factors.
◼Environmental triggers: exposure to viruses:
Epstein-Barr virus and those that cause measles,
herpes, chickenpox, or influenza.
◼Pathophysiology: In MS, antibodies and white
blood cells in the immune system attack myelin,
causing inflammation and injury to the sheath and
eventually the nerves that it surrounds. Loss of
myelin leads to leakage of K+ through voltage-gated
channels, hyperpolarization, and failure to conduct
action potentials.

48. ◼Signs & Symptoms: Paraparesis (weakness in
lower extremities) paraesthesia; numbness;
urinary incontinence; and heat intolerance.
◼Clinical examination shows optic neuritis,
characterized by blurred vision, a change in
colour perception, visual field defect (central
scotoma), and pain with eye movements;
dysarthria; and dysphagia.

Multiple Sclerosis (MS):

49. ◼Course of the disease is variable:
1.Relapsing-remitting MS: Transient episodes
appear suddenly, last a few weeks or months,
and then gradually disappear. Subsequent
episodes can appear years later. Full recovery
does not occur.
2.Secondary-progressive MS: A steadily
worsening course with only minor periods of
remission.
3.Primary-progressive MS: Progressive form
of the disease in which there are no periods of
remission.

Multiple Sclerosis (MS):

50. ◼Diagnosing: MS is very difficult and
generally is delayed until multiple episodes
occur.
1.Nerve conduction tests can detect
slowed conduction in motor and sensory
pathways.
2.Cerebral spinal fluid analysis can detect
the presence of oligoclonal bands
indicative of an abnormal immune
reaction against myelin.
3.Magnetic resonance imaging (MRI) to
visualize multiple scarred (sclerotic)areas
or plaques in the brain.

Multiple Sclerosis (MS):

51. “Iman Ali 'unable to speak' during interviews
due to rare disease”
◼Former supermodel and film actor Iman Ali opened up
about the challenges and difficulties she faces in
everyday life being a patient of multiple sclerosis — a
rare disease — in the Geo News programme "Hasna
Mana Hai".

52. “Iman Ali 'unable to speak' during interviews
due to rare disease”
◼Sharing details about her illness, she said one of the challenges is
difficulty with speech. The Bol starlet said sometimes she can't even
speak during interviews."Giving interviews is very difficult for me
because I slur a lot, I slur all the time," she said. The Khuda Kay
Liye star — who was diagnosed with MS in 2006 — said that the
disease never goes away and she has been trying to cope with it since
then."It is very difficult to explain what multiple sclerosis is," she
exclaimed. She said she had gone blind, lost the ability to walk, forgets
basic words and currently, her hands are numb for the last one and a
half year "but I see it as a challenge"."The best could be not to let it get
on your head, as many people have such diseases which are not
physically apparent," the film star said. She reiterated that speaking
during interviews was toug as compared to acting, which was easier for
her.

53. “Iman Ali 'unable to speak' during interviews
due to rare disease”
◼Iman Ali narrates her own experience of struggling with
Multiple Sclerosis. Since her diagnosis, nothing felt the
same to the renowned superstar but she never gave up.
She joined Lets Beat MS to spread awareness about the
disease to guide the MS warriors, so no one else would
face the same difficulties and isolation. Remember, early
diagnosis and treatment can help you defy all odds and
fight MS like a warrior.
◼Sources: The News April 5
th

2023,https://www.letsbeatms.pk/understanding-multiple-sclerosis-ms/

55. By the end of this lecture
you should be able to:

MS-P
005
Classify neurons functionally.

Classify nerve fibers according to
Erlanger & Gasser Classification
4

56. Functional classification of
neurons:

◼Neurons can be classified into three groups depending
on their functions:
1.Sensory neurons: Transmit the information from sensory
organs, like the skin, joints, eyes, ears, nose, tongue, and
towards the central nervous system. They are usually
unipolar neurons.
2.Interneurons: Receive, process, store and retrieve
information in the central nervous system. They can transfer
signals between sensory and motor neurons but can also
connect to each other. They are usually multipolar neurons.
3.Motor neurons: Carry outgoing signals towards the central
nervous system's muscles, organs, and glands. There are
usually multipolar neurons.

58. Morphological classification of
neurons:

◼Based on the number of processes that originate from
their cell body:
◼A) Unipolar neurons have one process, with different segments
serving as receptive surfaces and releasing terminals.
◼B) Bipolar neurons have two specialized processes: a dendrite that
carries information to the cell and an axon that transmits information
from the cell.
◼C) Some sensory neurons are in a subclass of bipolar cells called
pseudo-unipolar cells. As the cell develops, a single process splits
into two, both of which function as axons—one going to skin or
muscle and another to the spinal cord.
◼D) Multipolar cells have one axon and many dendrites. Examples
include motor neurons, hippocampal pyramidal cells and cerebellar
Purkinje cells.

60. Nerve fibers can be classified based on
different criteria:

◼1. Histologically, as myelinated or non-myelinated.
◼2. Functionally, as afferent (sensory) or efferent (motor).
◼3. Based on diameter and conduction velocity which is known
as Gasser and Erlanger’s classification.
◼4. Based on the type of neurotransmitter released from their
terminals as adrenergic, cholinergic, dopaminergic, etc.

Erlanger & Gasser Classification of nerve fibers:
◼Mammalian nerve fibers are divided into A, B, and C groups, and
the A group can be subdivided into α, β, γ, and δ fibers.

61. In general, the greater the diameter of a given nerve fiber, the
greater its speed of conduction.
The large axons are concerned primarily with proprioceptive
sensation, somatic motor function, conscious touch, and
pressure.
The smaller axons subserve pain and temperature sensations
and autonomic function.

62. Numerical Classification of
sensory nerve fibres:

◼A numerical system (Ia, Ib, II, III, and IV) is often used to
classify sensory fibers based on their axonal diameter and
conduction velocity:

63. Properties of nerve fiber
◼Excitability
◼Conductivity
◼Resting membrane potential (RMP)
◼All or none Law

64. Excitability
◼“Ability to respond to stimuli”
◼Stimulus is any change in environment which when
applied to cell body or nerve fiber results into stimulation
◼Types of stimuli:
1.Electrical
2.Mechanical
3.Thermal
4.Electro-magnetic
5.Chemical
End-result is action potential (nerve impulse) in nerve fiber

65. Nerve impulse
◼“It is electrochemical change which is
conducted along a nerve fiber
◼Stimulation/excitation depends upon:
1.Intensity of stimulus
2.Rate of stimulus
3.Time/duration of stimulus

66. Regarding intensity it may
be
◼Sub-threshold: minimal or less than threshold
◼Threshold : minimal required to stimulate
◼Supra-threshold: more than threshold
◼Generally when strength of stimulus increases,
duration required decreases

68. Two units of excitability
◼Rheobase: Strength or voltage of stimulus which
when applied to the tissue just excites it. The time
for which the stimulus is to be applied is called
utilization time
◼Chronaxie: It is the time or duration for which a
stimulus double than Rheobase when applied just
excites the tissue

69. Draw on sketch book!!

70. ◼Different tissues have different Chronaxie values:
1.Group A nerve fibers….0.1-0.2 msec
2.Skeletal muscle……..0.25-1 msec
3.Cardiac muscle…1-3 msec
◼Tissues, which are more excitable, have a shorter
Chronaxie value. So group A nerve fibers are
most excitable and cardiac muscle fibers are
least excitable
◼Clinical significance:
1.Chronaxie value helps the neurosurgeon to
access recovery after repair surgery
2.Chronaxie increases in myopathy

72. Refractory period
◼“The period during which the tissue does not
respond to second stimulus after the application
of the first stimulus”
◼It has 2 components:
1.Absolute RP: The portion of RP in which the
tissue does not respond at all to the 2
nd
stimulus,
whatever the strength of the stimulus may be
2.Relative RP: The tissue may respond to the 2
nd

stimulus if it is of higher intensity

74. ◼When we apply a stimulus, depending upon
strength, it may be a local excitatory state or
action potential (AP)
◼Sub-threshold --------?????? local excitation
◼Threshold or supra-threshold -----??????propagated AP

75. All or none law
◼On applying a stimulus, either the nerve fiber
does not produce an action potential (e.g.
sub-threshold) or it responds by producing a full
fledged action potential (e.g. By threshold or as
by supra-threshold stimulus)

77. Integral proteins in cell
membrane form channels
◼There are 3 types of channels
1.Leak channels
2.Voltage gated channels
3.Ligand/chemical gated channel

78. 1.Leak channels
◼K+ leak channels
◼K+Na+ leak channels

◼Leak channels are open all the time

79. 2.Voltage gated channels
◼These have got gates which open or close
according to voltage changes
◼These include:
1.Voltage gated Na+
2.Voltage gated K+
3.Voltage gated slow Ca++Na+
4.Voltage gated Ca++
5.Voltage gated Cl-
◼These channels are closed at rest and these are
opened during activity i.e. Action potential

80. 3.Ligand/chemical gated
channels
◼These open or close when a ligand or chemical
binds with receptor portion of protein
◼Ligand is a neurotransmitter or a hormone e.g..
Acetylcholine gated channels
◼These also open in activity (AP) and closed at rest

81. Electrogenic pump
◼In the cell membrane there is Na+K+ pump
called electrogenic pump
◼It maintains cell volume
◼It is active all the time (while resting or active
state)

82. Channels open at rest are
◼Leak channels
◼Na+K+ Pump

◼Which Channels are open in activity state (when
there is nerve impulse)???

84. By the end of this lecture
you should be able to:

MS-P
001
Explain the Physiological basis of membrane
potential
Explain diffusion potentials of Na & K

Define Nernst potential
Explain Physiological Basis of Nernst potential

Write the Nernst equation.
Calculate Nernst potential for Na & K

Explain the effects of altering the concentration
of Na+, K+, Ca on the equilibrium potential for
that ion
5

85. Diffusion potential is caused
by ion conc. Diff on the two
sides of the membrane
•K+ conc inside = 140 meq/l
•K+ conc outside= 4 meq/l
•Strong tendency of extra K+ ions to
diffuse out. As they do, they carry +ve
charge to the outside thus creating
electronegativity inside the membrane
because of negative anions that do not
diffuse out
•The diffusion potential becomes great
enough to block further net K+ diffusion
to the exterior
•The potential difference required is about
94 mV with negativity inside the
membrane

86. Diffusion potential
•Na+ outside = 142 meq/l
•Na+ inside = 14 meq/l
•Diffusion of positively charged Na+ ions to
the inside creating negativity outside and
positivity inside
•The membrane potential rises high enough
to block further net diffusion of Na+ to the
inside
•The potential is about 61 mV with positivity
inside the fiber

87. Nernst potential: relation of
the diffusion potential to the
concentration difference
◼“The diffusion potential level across a membrane
that exactly opposes the net diffusion of a
particular ion through the membrane is called
Nernst potential”

◼ Z
◼Z is electrical charge of the ion. Eg. +1 for K
+

◼The greater this ratio, the greater the tendency
for the ion to diffuse in one direction, and thus
greater the Nernst potential required to prevent
net diffusion

89. By the end of this lecture
you should be able to:

MS-P 002Describe the normal distribution of Na+, K+, Ca
and Cl- across the cell membrane
Explain physiological basis of Goldman
equation
Clarify the role of Goldman equation in
generation of RMP.
6

90. Resting Membrane Potential
(RMP)
◼“It is the potential difference across cell
membrane at rest”
◼All living cells have got RMP in their membranes
◼It is inside negative with respect to outside
◼Inside –ve ions more
◼Outside +ve ions more

91. Different tissues have
different RMP
◼Nerve fiber= -70 mV
◼Cell body of neuron= -65 mV
◼Skeletal muscle= -90 mV
◼Cardiac muscle= -85 mV
◼Smooth muscle= -50 to -60 mV
◼SA node fibers= -55 to -60 mV

92. How to record RMP
◼A microelectrode is introduced into the nerve
fiber or the cell, and another electrode is placed
on the surface of nerve fiber
◼Both electrodes connected to a measuring
apparatus to record potential difference
◼The microelectrode introduced into the cell is
called as silver-silver chloride electrode
◼It is made up of silver and contains AgCl2 solution

94. Mechanism of RMP
◼Ionic concentration inside and outside the cell:
◼A nerve fiber has 140 meq/L of K+ inside the cell.
Outside the cell is 4meq/L. so K+ is 35 times
greater inside the cell
◼Na+ inside the cell is 14 meq/L. outside it is 142
meq/L. Na+ is 10 times greater outside the cell
◼So there is 35 times gradient for K+ to diffuse out
and 10 times gradient for Na+ to leak in

95. 1.Contribution of K+ diffusion
potential
◼The main mechanism of RMP is outward diffusion of K+ through K+leak
channels
◼At rest the K+ leak channel is 100 times more permeable to K+ as
compared to Na+
◼So K+ leaks out through diffusion and this creates electronegativity inside
the cell. Using Nernst equation:
◼E (mV)= -61 log conc. Inside/conc. Outside
◼ = -61 log 140/4
◼ = -61 log 35
◼ = -61 x 1.54
◼ = -94 mV
◼Therefore, if K+ were only factor causing the RMP, then it would be equal
to -94 mV

96. 2.Contribution of Na+
diffusion through the nerve
membrane
◼There is only slight permeability of the membrane
to Na+ ions. Using Nernst equation:
◼E(mV)= -61 log conc. inside/conc. Outside
◼E(mV)= -61 log 14/142
◼ = -61 log 0.1
◼ = -61 x -1
◼ = +61 mV

97. Goldman equation
◼Nernst potential for K+ = -94 mV
◼Nernst potential for Na+ = +61 mV
◼How do these two interact with each other? We
use Goldman equation
◼It is also called Goldman Hodgkin Katz equation
◼E(mV)=


C=concentration i= inside
P= permeability o= outside

98. ◼If we solve this equation, RMP comes to -86 mV.
◼There is contribution by different ions ( Na+, K+
and Cl-)
◼In normal nerve fiber, the permeability of
membrane to K+ is 100 times more as compared
to Na+
◼The value from Goldman equation gives
potential inside the membrane of -86 mV, which
is near the K+ potential
◼So the major ion responsible for RMP is K+

99. 3.Contribution of Na
+
-K
+

pump
◼Continuously pumps 3 Na+ out and 2 K+ in
◼Continuous loss of positive ion from inside the cell
◼Electronegativity of -4mV
◼In summary, diffusion potentials caused by Na+
and K+ give a membrane potential of about -86
mV
◼Na+-K+ pump contributes -4 mV
◼So RMP= (-86) + (-4) = -90 mV

100. Establishment of resting
membrane potentials under
three conditions.
A, When the membrane
potential is caused entirely by
potassium diffusion alone.
B, When the membrane
potential is caused by diffusion
of both sodium and potassium
ions.
C, When the membrane
potential is caused by diffusion
of both sodium and
potassium ions plus pumping of
both these ions by the Na+-K+
pump
Draw in sketch book!

101. By the end of this lecture
you should be able to:

MS-P 003
Medical
Physiology
integrate
with
Anaesthesi
ology
Describe the Physiological basis of generation
of RMP.

Explain the effects of hyperkalemia and
Hypokalemia on the RMP

Name the membrane stabilizers
Explain the physiological basis of action of
Local Anaesthetics
7

102. Evidences that prove that outward K+
diffusion is the major factor involved in
RMP?

◼Changes in K+ conc. In ECF have marked effect
on RMP
◼In Hypokalemia (K+ < 4 mEq/L in ECF) , RMP
becomes more negative. This is called
hyperpolarization
◼In Hyperkalemia (K+ > 6meq/L in ECF) , RMP
decreases. This is called hypopolarization.
◼Changes in Na+ conc. In ECF do not have
significant effect on RMP

103. Bernstein Hypothesis
◼“The resting membrane potential is due to
spontaneous efflux of K+ ions”
◼Early 1900’s Julius Bernstein suggested that RMP
was equal to the potassium (Nernst) equilibrium
potential

104. Local Anaesthesia:
◼Local or regional anaesthesia is used to block the
conduction of action potentials in sensory and motor
nerve fibres. This occurs as a result of blockade of
voltage-gated Na+ channels on the nerve cell
membrane. This causes a gradual increase in the
threshold for excitability of the nerve, a reduction in the
rate of rise of the action potential, and a slowing of
axonal conduction velocity.
◼There are two major categories of local anaesthetics:
ester-linked (e.g., cocaine, procaine, tetracaine) or
amide-linked (e.g., lidocaine, bupivacaine).
◼Application of these drugs into the vicinity of a central
(e.g., epidural, spinal anaesthesia) or peripheral nerve
can lead to rapid, temporary, and almost complete
interruption of neural traffic to allow a surgical
procedure to be done without eliciting pain.

105. Local Anaesthesia:

◼Cocaine (from the coca shrub) was the first
chemical to be identified as having local
anaesthetic properties and remains the only
naturally occurring local anaesthetics. It’s
addictive and toxic properties prompted the
development of other local anaesthetics.
◼Nociceptive fibres (unmyelinated C fibres)
are the most sensitive to the blocking effect
of local anaesthetics. This is followed by
sequential loss of sensitivity to temperature,
touch, and deep pressure. Motor nerve fibres
are the most resistant to the actions of local
anaesthetics.

107. By the end of this lecture
you should be able to:

MS-P
006
Define Action Potential

Enlist the Properties of action potential

Describe the ionic basis of an action potential.

Explain the phases of action potential.

Explain the effects of hyperkalemia and
Hypokalemia on the action potential.

Draw monophasic action potential.

Explain absolute and relative refractory period
8

108. Action Potential (AP)
◼“Abrupt pulse like change in the
membrane potential lasting for fraction
of a second”
◼When we say a nerve impulse is
conducted along a nerve fiber, it
means AP is conducted along nerve
fiber.
◼We can see and record action
potential by cathode ray oscilloscope

109. Properties of AP
◼Abrupt and sudden in onset
◼It has a limited amplitude/magnitude
◼It is of short duration which is in msec
◼Obeys “all or none law”. If there is a threshold stimulus AP
is produced with maximum amplitude. If it is sub-threshold
stimulus, it is not produced at all. If stimulus is
supra-threshold there is no increase in amplitude of AP
◼It has got a refractory period
◼It is self propagating. Once produced in the cell
membrane it is automatically propagated in both
directions

110. AP has two main phases
◼Depolarization or rapid upstroke
◼Sudden loss of the normal negative membrane
potential inside nerve fiber is depolarization
◼Repolarization or rapid down stroke
◼Return of normal negative membrane potential
inside nerve fiber is repolarization

111. Draw in sketch book!

112. Mechanism of generation of
AP
◼Depolarization: involvement of fast voltage gated
Na+ channels
◼due to activation of these fast Na+ channels, these
open and there is rapid Na+ influx
◼So loss of negativity inside the membrane causes
depolarization
◼Size 0.5 mm x 0.3 mm, protein in nature
◼It has 2 gates
1.Activation gate on outer side
2.Inactivation gate on inner side

113. (−70 mV)
(−70 mV)
(−70 to +35 mV) (+35 to −70 mV,
delayed)
(+35 to −70 mV,
delayed)

114. At rest: activation gate is
closed and inactivation
gate is open
◼If nerve fiber in RMP, and we give a threshold
stimulus, it causes a conformational change in
the activation gate of Na+ channel, and this
causes opening of Na+ channel
◼Now the membrane permeability for Na+
increases markedly
◼Inside becomes +35 mV from RMP -70mV
◼It is sudden loss of negativity inside membrane or
depolarization

115. When conformational
change occurs the gate
opening is slow but then it
becomes very rapid at
-55mV
◼So at -55mV there is complete opening of Na
channel
◼So -55 mV is called threshold of activation or firing
level
◼For depolarization to occur, the membrane
potential must become -55mV

116. ◼Activation of Na+ channels involves a positive
feedback mechanism which causes progressively
more and more opening of Na+ channels
◼Activation of Na+ channels is short lived. It
remains for fraction of a second and then there is
inactivation d/t closure of inactivation gate
◼When inactivation gate closes, there is end of
depolarization
◼Inactivation gate will NOT reopen till RMP
become -70 mV or near the RMP

117. Repolarization
◼It is return of normal negative RMP
◼It is due to activation of voltage gated K+
channels
◼These have only one gate which is on the inner
side
◼Gate of K+ channel is closed at rest (-70 mV)
◼When there is application of stimulus which
causes opening of fast Na+ channels, a slow
change also starts in the gate of K+ channels but
very slowly

118. (−70 mV)
(−70 mV)
(−70 to +35 mV) (+35 to −70 mV,
delayed)
(+35 to −70 mV,
delayed)

119. These K+ channels open
when Na+ channels are
closing because of this slow
change
◼there is rapid K+ efflux
◼So +ve ions move out and repolarization occurs
due to loss of K+ ions

120. After-depolarization
◼When repolarization is about 70% completed its
rate becomes slow.
◼Cause is due to accumulation of K+ outside the
nerve fiber membrane so its further efflux is
slowed down

121. After- hyperpolarization
◼When the membrane potential reaches RMP
-70mV it does not stop there, but continues to
repolarize
◼Two causes:
1.When membrane potential after repolarization
reaches to the normal resting value, some K+
channels are still open and K+ efflux continues
2.Na+K+ pump is active all the time and
pumping out 3 Na+ and pumping in 2 K+

123. 9

124. - 55 mV is threshold of
excitation
◼“The portion of AP between firing level and start
of after-depolarization is called spike potential”
◼In nerve fiber and skeletal muscle there is spike
potential but in cardiac muscle and smooth
muscle there is AP with plateau

125. Absolute refractory period
◼During depolarization and first 1/3
rd
of
repolarization there is absolute refractory period
◼Reason: No strength or force of stimulus can
reopen the inactivation gate of Na+ channel till
the membrane potential is near the RMP

126. Relative refractory period
◼From the end of 1/3
rd
of repolarization to the start
of after-depolarization there is relative refractory
period
◼During relative refractory period the nerve fiber
may respond to second stimulus if it is stronger or
high intensity
◼In this period the membrane potential is
becoming near to RMP, so stronger stimulus can
reopen the inactivation gate of voltage gated
Na+ channel
◼The K+ channels are still open in this relative RP

128. Super-normal period
◼During after depolarization there is super-normal
period. The tissue is early to be excited and there
is decreased threshold of excitation, because it is
easy to reach the firing level

129. Sub-normal period
◼During after hyper-polarization there is more
negative RMP. So during this period the tissue is
difficult to be excited and this is called
sub-normal period
◼There is increased threshold of excitation and
more difficult to reach firing level

131. ◼When there is a series of action potentials, there is
chance of ionic disturbances, but Na+K+ pump
controls the correction of ionic balance
◼To reverse back ionic balance this pump works
by utilization of ATP
◼In unmyellinated nerve fiber there is point to point
conduction
◼In myellinated there is node to node conduction,
so only nodes depolarize and repolarize, so only
portions have ionic disturbances and energy as
ATP is conserved as lesser ionic disturbance

132. Evidences to prove the
mechanism of AP
◼First we inject radioactive Na+ into ECF
◼And then we stimulate the nerve fiber to produce
AP
◼We can detect radioactive Na+ inside the nerve
fiber

133. Evidences to prove the
mechanism of AP
◼Second we take out a nerve fiber form the body
and place it in Na+free isotonic solution.
◼A threshold stimulus is applied to a nerve fiber
◼Action potential is not produced because there is
no Na+ outside

134. Evidences to prove the
mechanism of AP
◼Third is voltage clamp experiment
◼There are two electrodes
1.Voltage electrode to measure voltage
2.Current electrode to inject +ve or –ve current
◼There is oscilloscope to see/ record AP (cathode ray
oscilloscope)
◼We want to produce a desired voltage inside nerve
fiber from RMP of -70 mV to +10 mV
◼This is done by injecting current from current
electrode

135. Evidences to prove the
mechanism of AP
◼Voltage is produced by ionic movement and
maintained by Na+ influx
◼Now if we again shift from +10 to -70mV it will
involve current injection and then maintenance
of voltage at -70mV by K+ efflux

136. Evidences to prove the
mechanism of AP
◼Fourth : certain toxins e.g.. Tetrodotoxin when
applied on the outer side of cell membrane
blocks the voltage gated Na+ channels. Then if
nerve fiber is stimulated there will be NO Action
Potential
◼Tetra-ethyl-ammonium another toxin when
applied to inner side of cell membrane blocks
the K+ channels. So there will be NO
repolarization

138. By the end of this lecture
you should be able to:

MS-
P
007
Explain the role of other
ions in action potential.

Elaborate the effect of
hypocalcemia on neuron
excitability.
10

139. Role of Ca++ in membrane
excitability
◼Ca++ stabilizes the cell membrane
◼The inner side of voltage gated Na+ channel has a strong
negative charge
◼Ca++ in the ECF binds with the negatively charged inner
surface of Na+ channel to close them. So activation gates
of channels completely closed at rest


◼In HYPOCALCEMIA ionic Ca++ in ECF decreases, so
activation gates of Na+ channel are not completely
closed at rest, there is leakage of Na+ into the nerve fiber.
This decreases the threshold of excitation resulting into
hyper excitability of nerves called tetany

140. Tetany
◼There is carpo-pedal spasm, spasm of respiratory
muscles.
◼When motor nerves become hyper excitable
then muscle spasms
◼If sensory nerves become hyper excitable then
parasthesia or abnormal sensation

141. Role of other ions in
membrane excitability

◼Hypokalemia: Hyperpolarization of RMP and
decreased excitability
◼Hyperkalemia: Hypopolarization of RMP and
increased excitability
◼Changes in serum chloride and sodium ion
concentrations do not effect much.

142. By the end of this lecture
you should be able to:

MS-
P
010
Explain the mechanism of
conduction of Nerve impulse in
myelinated and unmyelinated
nerve fibers.

Elaborate significance of saltatory
conduction
10

143. ◼Action potential produced is propagated:
1.Propagation of AP in unmyellinated nerve fiber
2.Propagation of AP in myellinated nerve fiber

144. Propagation of AP in
unmyellinated nerve fiber

◼Unmyellinated nerve fiber at RMP is polarized
◼We apply a threshold stimulus
◼Inside becomes positive and outside becomes
negative
◼AP is self propagating
◼The depolarized point has adjacent polarized
point
◼A local circuit of current flow is established b/w
the depolarized point and the adjacent
polarized point
◼This current flow is in the axoplasm and ECF

145. ◼The current flowing out through the polarized
point opens or activates the Na+ channels
◼So Na+ influx occurs and the point now becomes
depolarized
◼A new local circuit of current is formed between
the newly depolarized point and the polarized
point
◼So there is point to point propagation of AP by
forming local circuit of current b/w the
depolarized point and adjacent polarized point
◼This occurs in both directions simultaneously

146. ◼This is how whole length of fiber becomes
depolarized. Inside the body propagation of AP
occurs in both directions but in nerve pathways
there are synapses which allow conduction only
in one direction, from pre-synaptic neuron to
post-synaptic neuron. So only forward direction
occurs

149. Propagation of AP in
myellinated nerve fiber
◼Myelin sheath is an insulator. It is absent at nodes
of Ranvier which only contain neurilemma with
ionic channels
◼In myelin sheath no ionic channels and it does
not let current flow
◼We apply threshold stimulus and node of Ranvier
becomes depolarized. Next node is polarized, so
local circuit of current is formed b/w the
depolarized and polarized node of Ranvier
◼The current flowing out through the depolarized
node activates Na+ channels of the adjacent
polarized node which now becomes depolarized

150. Saltatory conduction
◼So there is node-to-node propagation of AP .
Jumping of nerve impulse from node to node is
called Saltatory conduction.

◼Saltate-------to jump

154. How to prove saltatory
conduction in myelinated
Nerve Fiber
◼One by ringer bridge experiment
◼There are two containers A and B connected
through a tube which has a screw or stop cork
◼Containers are filled with ringer solution or normal
saline
◼We place a nerve fiber on this container in such
a way that A container has one node of Ranvier
and in B container another node of Ranvier
◼We stimulate nerve fiber to have AP

155. ◼When we open the screw, local circuit of current
flow b/w 2 nodes is completed and we can
record AP from beyond container B
◼When screw is closed, no local circuit, so no AP
recorded

◼Second we apply blocking drug like Cocaine on
the node, there is no conduction. When applied
to internode region, conduction occurs

156. Advantage of saltatory
conduction
◼Faster velocity of conduction:
Unmyelinated…velocity 0.5-5 m/sec
Myelinated……..velocity 120 m/sec
▪Thicker the nerve fiber, longer the internode and
faster the velocity of conduction
▪Velocity of conduction increases in myelinated
nerve fiber with increase in fiber diameter
▪Velocity of conduction increases in unmyelinated
nerve fiber with sq. root of fiber diameter

157. ◼Energy is conserved in saltatory conduction:
◼After AP, the NaK pump has to work more to
re-establish ionic balance.
◼In unmyelinated all fiber needs ionic balance
reestablished
◼But in myelinated only nodes need to be
corrected so it conserves ATP

158. Heat production in nerves
◼At rest only small amount of heat is liberated
◼When nerve is stimulated more heat is liberated
◼It is because of increased activity of Na-K-pump
to reestablish the Na+ and K+ concentration
difference
◼This “recharging” of nerve fiber is an active
metabolic process using ATP

159. Heat production in nerves

160. Orthodromic and
Antidromic conduction
◼The normal direction of current flow /conduction
along nerve fiber is orthodromic conduction.
◼E.g..
1.Sensory nerve from periphery to CNS
2.Motor nerve from CNS to periphery
◼Sometimes in body there is antidromic
conduction i.e. it occurs in a direction opposite
to normal direction
◼E.g.. Sensory nerve from CNS to periphery

162. Axon reflex
◼In some sensory nerve fibers there are collaterals
that work on antidromic conduction
◼Eg: Tripple response: skin scratched with sharp
object. Red line, wheel and flare formed.
◼Wheel and flare because of pain receptors that
transmit impulses along their axons in not only
normal orthodromic direction but also in
antidromic into neighboring skin to free nerve
endings that release substance P. it causes
arteries to vasodilate (Flare) and mast cells to
release histamine (wheel)

164. By the end of this lecture
you should be able to:

MS-
P
008
Explain Physiological basis &
properties of Graded potential

Draw & explain Physiological basis
& properties of compound action
potential.
11

165. Types of action potentials
◼Spike potential: nerve fiber
◼Action potential with plateau: in cardiac muscle
and smooth muscle. It has 3 phases:
1.Rapid depolarization
2.Plateau or sustained depolarization
3.Rapid repolarization

167. ◼Rapid depolarization: rapid Na+ influx d/t voltage
gated fast Na+ channels. Threshold = -55mV
◼Plateau phase: it is d/t sustained depolarization.
Slow influx of Ca++ and Na+ (L-type)through
voltage gated slow Ca++Na+ channels.
Threshold of activation is -40 mV. Duration is
about 300 msec
◼Why the potential drops at the beginning of
plateau phase?
1.Inactivation of fast Na+ channels
2.Some leakage of K+ through opening of K+
channels occurs. This leads to drop in positivity
◼Rapid repolarization: d/t rapid K+ efflux through
voltage gated K+ channels

168. ◼Duration of AP with plateau is 300-350 msec,
compared to nerve AP which is just few msec
◼So there is a long refractory period in smooth and
cardiac muscle
◼In skeletal muscle and nerve fiber there is short
refractory period
◼Most of the duration of AP in cardiac and smooth
muscle is because of plateau phase

169. Types of action potentials
◼Compound action potential: a multipeaked AP
recorded from a nerve trunk e.g. sciatic nerve
◼A nerve trunk has large no of nerve fibers having
variable diameter. Along these nerve fibers there
are different velocity of conduction. If we
stimulate a nerve trunk and at distance we place
recording electrodes:

170. Compound AP:
First peak is of fastest nerve fiber
Second of second fastest and so on
So multiple peaks in EMG

171. ◼Compound AP is the basis of Electro-physiological
classification of nerve fibers
◼Three main peaks are recorded:
1.A (A-alpha, A-beta, A-delta and A-gamma) (most
susceptible to pressure- Sunday morning paralysis)
2.B (most susceptible to hypoxia)
3.C (most susceptible to anesthetics)
◼A-alpha: thickest, having max velocity of conduction (70
– 120 m/sec)
◼A-delta: are slowest to conduct
◼A and B type are myellinated
◼C are unmyellinated
◼B are preganglionic autonomic
◼C are postganglionic autonomic

172. Stabilizers of membrane
excitability
◼Calcium ions in ECF stabilizes the cell membrane
◼High conc of Ca++ in ECF stabilizes the cell
membrane excitability or depress cell membrane
excitability. Ca++ binds with inner side of Na+
channels to close the activated gates. When
there is decreased Ca++, excitability increases as
gates do not close
◼Hypercalcemia: more tight closure of activation
gate, so this decreases the membrane
excitability

173. ◼There are certain other stabilizers :
◼Local anesthetics, such as cocaine(procaine,
tetracaine): these bind with the activation gate
and don’t let them open. So nerve impulse is not
propagated.
◼Safety factor: “it is the ratio b/w action potential
strength and excitability threshold.”
◼Normally it is = 1. When below 1, nerve impulse
fails to be conducted along nerve fiber.
◼Local anesthetics increase the excitability
threshold and safety factor becomes below 1 so
no AP

174. Cathode ray oscilloscope
◼Action potential is visualized by cathode ray
oscilloscope

176. By the end of this lecture
you should be able to:

MS-P
009
Classify and explain
Physiological basis of different
types of synapses

Elaborate how signal
transmission takes place
across chemical synapse
12

177. Synapse and Synaptic transmission

◼Synapse is a junction between two neurons or an inter-neuronal junction.
◼Anatomical Classification:
∙Axo-dendritic (80-90%)
∙Axo-somatic (5-20%)
∙Axo-axomal (very few)
∙Dendro-dendrtitic
∙Dendro-somatic
◼Functional Classification:
◼Chemical synapse
◼Electrical Synapse

179. Chemical synapse

◼Membrane of synaptic knob is called pre-synaptic membrane, and that of the second neuron is
post-synaptic membrane, and the space between these two is synaptic cleft which is 20-30 nm
(200-300 Angstroms). On post-synaptic membrane are receptor proteins. Each receptor protein has
two components:
∙Binding component which binds the neurotransmitter
∙Inophore component which is present throughout the thickness of the post-synaptic membrane and
consists of two parts:
1.Ion channel
2.Second messenger activator
◼Ion channels are of further two types:
1.Cation channels (Na
+
, K
+
)
2.Anion channels (Cl
-)

◼Excitatory neurotransmitter opens the Na
+
cation channel
◼Inhibitory neurotransmitter opens the Cl
-
ion channel. It can also open K
+
channel, which is cation
channel.

180. Second messenger activator:
◼The neurotransmitter binds with the receptor and causes activation of G-protein.
This G-protein results into activation of some enzymes or formation of second
messengers like cAMP and cGMP etc. it can also cause gene activation.
◼Through most of the synapses, transmission involves neurotransmitter but
through few there may be electrical transmission of impulses. The synapse acts
like a Gap junction, which contains Ion channels that have low electrical
resistance.
◼The nerve impulse reaches the synaptic knob and causes depolarization of the
membrane of synaptic knob. This leads to opening of voltage gated Ca
++
channels
and results into Ca
++
influx from ECF into synaptic knob. This Ca
++
binds with
release sites on the pre-synaptic membrane and causes opening of release sites
on the membrane. Some of the vesicles containing neurotransmitter fuse with
the release sites and rupture to release the neurotransmitter into the synaptic
cleft. The neurotransmitter diffuses towards the post-synaptic membrane where
it binds with the receptors. Binding results into a localized change in membrane
potential which is called post-synaptic membrane potential (PSP). Depending
upon the type of neurotransmitter and the type of channels opened, the
post-synaptic neuron is either excited or inhibited.

181. By the end of this lecture
you should be able to:

MS-P
008
Explain Physiological basis & properties of Graded
potential

Contrast between action potential and graded
potential.

Describe the ionic basis of excitatory post synaptic
potential (EPSP), inhibitory post synaptic potential
(IPSP), end plate potential (EPP).
12

182. ◼Post Synaptic Potential (PSP) is of 2 types:
∙Excitatory post-synaptic potential (EPSP)
∙Inhibitory post synaptic potential (IPSP)
◼Excitatory post-synaptic potential (EPSP): Resembles EPP
(end plate potential). Its voltage depends upon the amount of
neurotransmitter released. Significance; RMP of cell bodies of
neurons is -65 mV and threshold of excitation is -45mV. So, the
purpose of EPSP is to bring membrane potential from -65 to
-45 mV.

183. ◼Properties of EPSP:
1.Localized change
2.Non-propagative
3.Decremented with distance
4.Does not obey all or non law
5.Voltage proportional to the quantity of neurotransmitter
released (graded response)
6.No refractory period
7.Prolonged duration as compared to AP

184. ◼Inhibitory post-synaptic potential (IPSP): causes inhibition of
post-synaptic neuron. Inhibitory neurotransmitter is released.
Two types of channels open in the post-synaptic neuron: Cl
-

channels and K
+
channels. Influx on Cl
-
causes
hyperpolarization of the membrane (-70mV) and efflux of K
also cause hyperpolarization. Glycine is a neurotransmitter for
post-synaptic inhibition; duration of inhibition is 10-15 msec.
Pre-synaptic inhibition is brought about by GABA (gamma
amino butyric acid). This inhibition lasts for longer time
(minutes to hours). GABA also causes opening of Cl
-
channels
and K
+
channels so there is hyperpolarization in the
presynaptic knob by axo-axonal synapses.