Nerve Physiology

1. NERVE PHYSIOLOGY
DR SARAN AJAY
DEPT OF PHYSIOLOGY, GMCM

2. DEPT OF PHYSIOLOGY, GMCM 10
What is an excitable tissue?

3. Excitable Tissue
•Propertyofrespondingtoastimulusiscalled
excitabilityorirritability
•Asuddenandappreciablechangeinenvironment
oflivingmatter,lastingforaminimumtime
constituteastimulus
•Capableofgenerationofelectricalimpulsesat
theirmembranes

4. •These impulses are used to transmit signals along the
membranes
•Mainly 2 excitable tissues –Nerve & muscle
DEPT OF PHYSIOLOGY, GMCM 12

5. •Nerves-specializedforfunctionofreception,
integrationandtransmissionofinformationinthebody
•Muscles-alsoexcitabletissuesbutarecharacterized
bymechanicalcontraction
DEPT OF PHYSIOLOGY, GMCM 13

6. DEPT OF PHYSIOLOGY, GMCM 14
CNS : Central Nervous System
PNS: Peripheral Nervous System
NERVOUS SYSTEM

7. Cellular elements of CNS
•Neurons-basic building blocks
•10
11
neurons
•Also contain Glial cells
•40% of human genes participate in the formation of CNS

8. DEPT OF PHYSIOLOGY, GMCM 16

9. DEPT OF PHYSIOLOGY, GMCM 19
STRUCTURE
OF NEURON

10. DEPT OF PHYSIOLOGY, GMCM 20

11. Cell body/ Soma/ Perikaryon
1.Round , stellate, pyramidal, fusiform
2.Nucleus with nucleoli
3.No centrosome
4.Cytoplasm –mitochondria, ER, Golgi apparatus, Nissl
granules

12. 5.Nissl granules
•Basophilic granules
•Contains rough ER
•Involved in protein synthesis
•Absent from axon & axon hillock
•Chromatolysis-disintegrate and finally disappear
DEPT OF PHYSIOLOGY, GMCM 22

13. 7. Neurofibrils
•Microfilaments and Microtubules
•Alzheimer's disease: microfilament proteins →
neurofibrillary tangles
DEPT OF PHYSIOLOGY, GMCM 24

14. DEPT OF PHYSIOLOGY, GMCM 25

15. DEPT OF PHYSIOLOGY, GMCM 26

16. 8. Pigment granules
•Neuromelanin-in substantia nigra
•Lipofuscin-aging neurons
DEPT OF PHYSIOLOGY, GMCM 28

17. Site of cell bodies
•Gray matter of CNS
•Autonomic and posterior nerve root ganglia
Group of cell bodies
•Inside the CNS-Nucleus
•Outside CNS-Ganglia
DEPT OF PHYSIOLOGY, GMCM 30

18. Dendrites
•Small multiple branched processes
•Short course, irregular number
•Contains Nissl bodies
•Thorny projections –Dendritic spines
•Impulses travel towards the cell body
DEPT OF PHYSIOLOGY, GMCM 31

19. Axon
•Single long process
•Arise from Axon hillock
•Initial segment –first part of axon
•Axolemma and axoplasm
DEPT OF PHYSIOLOGY, GMCM 34

20. DEPT OF PHYSIOLOGY, GMCM 35

21. •Axon divides into presynaptic terminals, which end in
•Synaptic knobs/ terminal buttons/ axon telodendrion
•Carries impulses away from cell body
•Myelinated and unmyelinated nerve fibers
DEPT OF PHYSIOLOGY, GMCM 36

22. DEPT OF PHYSIOLOGY, GMCM 39
MYELINATION

23. DEPT OF PHYSIOLOGY, GMCM 40

24. Myelination in PNS
DEPT OF PHYSIOLOGY, GMCM 41

25. •Schwann cell -wraps its membrane around an axon up to
100 times
•Axons invaginate into cytoplasm of Schwann cell
•So becomes suspended in a fold of Schwann cell
membrane -mesaxon
DEPT OF PHYSIOLOGY, GMCM 42

26. DEPT OF PHYSIOLOGY, GMCM 44

27. •Lipids are deposited between the layers of Schwann cell
•Compacted to form myelin sheath –by Protein zero( P
0)
•Extracellular portions of this membrane proteins on the
apposing membranes lock to each other
•Mutations in the gene for P
0→Peripheral neuropathy
•Outermost cell membrane →Neurilemma
DEPT OF PHYSIOLOGY, GMCM 46

28. DEPT OF PHYSIOLOGY, GMCM 47

29. •Each Schwann cell provide myelin sheath for a short
segment of axon
•Between 2 segments -1µm constrictions –Nodes of
Ranvier
•Myelin is absent at axonal endings
DEPT OF PHYSIOLOGY, GMCM 48

30. Functions of Myelin
1.Increases velocity of conduction: Saltatory conduction
2.Reduces energy expenditure for conduction
3.Acts as an insulator –prevents cross stimulation
DEPT OF PHYSIOLOGY, GMCM 50

31. DEPT OF PHYSIOLOGY, GMCM 51

32. In unmyelinated nerves,
•Axon is surrounded by Schwann cell without wrapping of
membrane
DEPT OF PHYSIOLOGY, GMCM 52

33. Myelination in CNS
•Oligodendrocytesform myelin
•They extend multiple processes and form myelin on many
axons
DEPT OF PHYSIOLOGY, GMCM 53

34. DEPT OF PHYSIOLOGY, GMCM 54

35. Myelinogenesis
•Begins at 4
th
month of intra uterine life
•Sensory fibers –4
th
-5
th
month
•Pyramidal tract (motor fibers) –2 years
DEPT OF PHYSIOLOGY, GMCM 55

36. 1.Babinski Test in children –Extensor Response
2.Mutations in gene for Protein
0→Peripheral
neuropathies
DEPT OF PHYSIOLOGY, GMCM 56
Applied Aspects

37. 2. Multiple sclerosis -demyelinating disease
•Autoimmune
•Antibodies and WBCs attack myelin →
inflammation & injury to the sheath →eventually
the nerves are affected
DEPT OF PHYSIOLOGY, GMCM 58

38. •Loss of myelin →leakage of K
+
through voltage-gated
channels →hyperpolarization→failure to conduct
impulses
•Nerve conduction tests show slowed conduction in motor
& sensory pathways
•Numbness and weakness
•Optic neuritis
DEPT OF PHYSIOLOGY, GMCM 60

39. NERVE PHYSIOLOGY -2
DR SARAN AJAY
DEPT OF PHYSIOLOGY, GMCM

40. Specific Learning Objectives
•Functional Zones of a Neuron
•Classification of Neuron
•Transport and Metabolism
•Peripheral Nerve
•Nerve Injury and Degeneration
•Neuroglia
•Neurotropins

41. DEPT OF PHYSIOLOGY, GMCM 8
FUNCTIONAL
ZONES OF
A NEURON

42. DEPT OF PHYSIOLOGY, GMCM 9

43. Functional Zones of a Neuron
1.Receptor zone-dendritic zone-local potentials
2.Site of origin of conducted impulses
•Motor neuron –initial segment
•Sensory –1
st
node of Ranvier
3.Zone of all or none transmission-axon
4.Zone of secretion of neurotransmitters
DEPT OF PHYSIOLOGY, GMCM 10

44. Granules or vesicles –neurotransmitter
Termination
•Synapse
•Effecter organ (muscle or gland)
•Peripheral ganglion
DEPT OF PHYSIOLOGY, GMCM 11

45. CLASSIFICATION
OF NEURONS

46. Classification of neuron
1.Depending upon number of poles/ structural classification
2.Depending upon the function
3.Depending upon length of axon
DEPT OF PHYSIOLOGY, GMCM 15

47. A. Depending upon number of poles
1. Unipolar neuron
•Single pole
•Both dendrites and axon arise from that
DEPT OF PHYSIOLOGY, GMCM 16

48. DEPT OF PHYSIOLOGY, GMCM 17
2. Bipolar neuron
2 poles-one for axon, one for dendrite

49. 3. Pseudo unipolar neuron
•A subclass of bipolar cells
•A single process splits into two, both of which function as axons
•Peripheral one going to skin or muscle and central one to spinal
cord
•Eg: Dorsal root ganglion (DRG)
DEPT OF PHYSIOLOGY, GMCM 18

50. DEPT OF PHYSIOLOGY, GMCM 19

51. 4. Multi polar neuron
•One pole-axon
•Other poles-dendrites
DEPT OF PHYSIOLOGY, GMCM 20
Q. KUHS AUGUST 2015

52. DEPT OF PHYSIOLOGY, GMCM 21

53. B. Depending on function
1.Sensory /afferent neuron
2.Motor / efferent neuron
3.Interneuron
DEPT OF PHYSIOLOGY, GMCM 22

55. C. Depending upon length of axon
Golgi type 1-also known as projection neurons
•Have long axons
•Neurons forming peripheral nerves & long tracts of brain
Golgi type 2-short circuit neuron
•Short axons
•Numerous in cerebral cortex, cerebellar cortex, retina
DEPT OF PHYSIOLOGY, GMCM 24

56. Biological activities in a neuron
•Protein synthesis & transport
•Metabolism
•Excitation and conduction of impulses

57. Protein synthesis & Transport
•Soma is the machinery for protein synthesis
•Neurotransmitters and other proteins that are needed at the
axon terminals
•Transport of proteins and polypeptides to axonal ending
occurs by axoplasmic flow

59. Axoplasmic flow/ transport
1. Anterograde transport:from cell body →axon terminal
•Fast axonal transport-400mm/day
•Slow axonal transport-0.5-10mm/day

60. •Occurs along microtubules
•Requires 2 molecular motors
Dynein & Kinesin

63. Substances transported are
•Fast Axonal transport
1.Mitochondria and other membrane bound organelles
2.Small Vesicles
3.Actin and Myosin
•Slow Axonal Transport
1.Tubulins of microtubules
2.Protein subunits of neurofilaments

64. 2. Retrograde transport
•From axon terminal →cell body
•200mm/ day
•Occurs along microtubules

65. Substances transported are
1.Used synaptic vesicles,
2.Nerve growth factors (NGF)
3.Viruses like polio, herpes simplex and rabies
4.Toxins e.g.: tetanus toxin

68. Metabolism
•Low level
•70% total energy is used to maintain the polarity of membrane
•By action of Na
+
-K
+
ATPase
•At maximum activity–metabolic rate doubles

70. Peripheral Nerve
•Compact bundle of axons located outside CNS –Nerve
•Axons are arranged in different bundles –Fasciculi
•Each axon is covered by Endoneurium
•Each fasciculus is covered by Perineurium
•Whole nerve is covered by Epineurium

72. NERVE INJURY -
DEGENERATION
REGENERATION

73. Response to injury
Types of injury
•Cut injury
•Crush injury
•Ischemia
•Injection of toxic substance
•Diseases like DM, syphilis
•Pressure on the nerve

74. A. Physical and chemical degenerative changes
1.Axon distal to the injury (anterograde degeneration)
2.Proximal to the injury
3.Cell body
(retrograde degeneration)

76. 1. Anterograde degeneration (Wallerian)
•Axon distal to the injury
•Augustus Waller
Q. KUHS 2022 JULY

77. a)Changes in impulse conduction
b)Changes in the axon
c)Changes in the myelin sheath
d)Changes in the Neurilemma –Ghost tube

78. a. Changes in impulse conduction
1.If severed -stops within hours
2.If crushed
•Up to 3 days normal conduction
•After 3 days deteriorates seriously
•After 5 days no impulse evoked

79. b. Changes in Axon
1.Swells up
2.Irregular in shape
3.Breaks into small fragments
4.Axon terminals retract from post synaptic target
5.Within several weeks axon and its terminals degenerate

81. c. Myelin Sheath
1.Small fragments
2.Hydrolysis of myelin to fatty droplets
3.Begins by 8
th
dayand completed by 32days

82. d. Neurilemma
1.Intact
2.Schwann cells –increase size and multiply
3.Macrophages remove degenerating axons, myelin
and cellular debris
4.Neurilemmal tube becomes empty –Ghost tube

83. 2. Retrograde degeneration
•Proximal to injury
•Similar to changes seen in distal part of axon
•Occurs only up to first or second node of Ranvier
•Changes seen in proximal part of axon along with those
in cell body constitute retrograde degeneration

84. 3. Changes in cell body
•Starts within 48hr→continues up to 15-20 days
•Cell organelles are fragmented and eventually disappear
•Cell body draws in more fluid, swells up
•Nissl substances undergo Chromatolysis
•Nucleus is displaced to periphery and extruded out of cell

85. B. Regeneration
Under favorable conditions
•Neurilemma present
•Cell body & nucleus are intact
•Gap less than 3mm
•Sliced cut, cut ends in straight line

86. •Starts within 4 days of injury
•More active after 30 days
•Complete recovery-several months to one year
•1 –4 mm per day

87. Changes in the axon
•From proximal stump axon elongates and give out fibrils
•Schwann cells of distal end guide the fibril to enter the endo
neural tube
•Fibril makes contact with the peripheral end organ
•Myelination –completed in 1 year
•80% of original diameter is regained

89. Changes in the cell body
•20-80d
•Nissl granules followed by Golgi apparatus appear in
cell body
•Cell loses excess water, regains its normal size
•Nucleus occupies the central position

93. Complication following nerve injury
1.Complete atrophy
2.Functional complications-misinterpretation of
sensations
3.Neuromaformation-if fibrils could not find distal cut
end, it will form a mass

94. 4. Phantom Limb
•Feeling perceived by a patient after amputation of limb
•Neuroma when stimulated, patient feel the lost limb

95. Phantom Limb / Pain

96. NERVE PHYSIOLOGY -2b
DR SARAN AJAY
DEPT OF PHYSIOLOGY, GMCM

97. Specific Learning Objectives
•Functional Zones of a Neuron
•Classification of Neuron
•Transport and Metabolism
•Peripheral Nerve
•Nerve Injury and Degeneration
•Neuroglia
•Neurotropins

98. Glial cells/ Neuroglia
•Supporting cells in nervous system
•2 types: Microglia& Macroglia
•Microgliaarise from macrophages
•Act as scavenger cells –remove debris resulting from
injury, infection, and diseases

99. •Macroglia:Oligodendrocytes, Schwann cells, & Astrocytes
•Oligodendrocytes
•In white matter provide myelin
•In gray matter support neurons
•Schwann cells provide myelin to PNS
•Astrocytesmost common glia in the CNS, star like shape

102. Astrocytes
Astrocytes help to regulate the microenvironment in CNS
under normal conditions and also in response to damage.

103. •Fibrous
•contain intermediate filaments
•found in white matter
•Protoplasmic–found in gray matter

104. Functions
•Astrocytes send processes to blood vessels →induce
capillaries to form tight junctions →Blood–brain barrier
•Also send processes that envelop synapses and surface
of nerve cells
•Produce neurotropins

106. •Help to maintain concentration of ions and neurotransmitters
•Regulate microenvironment of neuron
•Membrane potential of protoplasmic astrocyte varies with
external K
+

108. Specific Learning Objectives
•Functional Zones of a Neuron
•Classification of Neuron
•Transport and Metabolism
•Peripheral Nerve
•Nerve Injury and Degeneration
•Neuroglia
•Neurotropins

109. Neurotrophins
•Proteins necessary for survival and growth of neurons
•Site of production-muscles, structures innervated by
neuron, astrocytes, neurons
•Retrograde transport and Anterograde transport

110. Nerve growth factor (NGF)
•First neurotrophinidentified
•Sympathetic nerves, sensory nerves
•Trk A Receptor
Brain derived neurotrophic factor (BDNF)
•Trk B
•Peripheral sensory nerves

111. Neurotrophin-3
•Trk B and Trk C
•Cutaneous mechanoreceptors
•Proprioceptor neurons that innervate muscle spindle

112. Specific Learning Objectives
•Functional Zones of a Neuron
•Classification of Neuron
•Transport and Metabolism
•Peripheral Nerve
•Nerve Injury and Degeneration
•Neuroglia
•Neurotropins

113. NERVE PHYSIOLOGY -3
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM

114. Hodgkin and Huxley
Nobel Prize in Physiology
and Medicine 1963

115. Specific Learning Objectives
•Membrane Potential
•Resting Membrane Potential
•Genesis of RMP
•Electrotonic Potentials
DEPT. OF PHYSIOLOGY, GMCM 7

116. MEMBRANE
POTENTIAL
DEPT. OF PHYSIOLOGY, GMCM 8

117. •The potential difference across the membrane of all living
cells
•Results from the separation of chargesacross the cell
membrane
DEPT. OF PHYSIOLOGY, GMCM 9

118. +
DEPT. OF PHYSIOLOGY, GMCM 10

119. DEPT. OF PHYSIOLOGY, GMCM 11

120. DEPT. OF PHYSIOLOGY, GMCM 12

121. •Note that the membrane itself is not charged.
•The term membrane potential refers to the difference in charge
between the wafer-thin regions of ICF and ECF lying next to the
inside and outside of the membrane, respectively.
DEPT. OF PHYSIOLOGY, GMCM 13

122. DEPT. OF PHYSIOLOGY, GMCM 14

123. 1.Transport processes
2.Signaling purposes
DEPT. OF PHYSIOLOGY, GMCM 16

124. •The energy stored in this miniature battery can drive a variety of
transmembrane transport processes.
•Electrically excitable cells such as brain neurons and heart
myocytes also use this energy for signalling purposes. The brief
electrical impulses produced by such cells are called action
potentials.
DEPT. OF PHYSIOLOGY, GMCM 17

125. More the separation of charges, more is the membrane potential.
DEPT. OF PHYSIOLOGY, GMCM 18

126. •The inside is negative with respect to the outside
•Varies from cell to cell
•Varies with functional status
DEPT. OF PHYSIOLOGY, GMCM 19

127. •The cells of excitable tissues—namely, nerve cells and muscle
cells—have the ability to produce rapid, transient changes in their
membrane potential when excited.
•These brief fluctuations in potential serve as electrical signals or
action potentials.
DEPT. OF PHYSIOLOGY, GMCM 20

128. Specific Learning Objectives
•Membrane Potential
•Resting Membrane Potential
•Genesis of RMP
•Electrotonic Potentials
DEPT. OF PHYSIOLOGY, GMCM 22

129. •It is the potential difference across the membrane while the
cell is at rest.
Neuron : -70mV
Skeletal & cardiac muscle: -90mV
RBC : -10mV
•Transmembrane / Steady state potential / Diffusion potential
Resting Membrane Potential
DEPT. OF PHYSIOLOGY, GMCM 23

130. •The constant membrane potential present in the cells of non excitable
tissues and those of excitable tissues when they are at rest—that is,
when they are not producing electrical signals—is known as the
resting membrane potential.
DEPT. OF PHYSIOLOGY, GMCM 24

131. Recording of RMP
DEPT. OF PHYSIOLOGY, GMCM 25

132. •Microelectrodes
•Amplifier
•Voltmeter
•Cathode Ray Oscilloscope (CRO) for rapid changes
Equipment
DEPT. OF PHYSIOLOGY, GMCM 26

133. Specific Learning Objectives
•Membrane Potential
•Resting Membrane Potential
•Genesis of RMP
•Electrotonic Potentials
DEPT. OF PHYSIOLOGY, GMCM 28

134. Genesis of RMP
•Due to the unequal distribution of ions across the cell
membrane (concentration gradient)
•Their selective movementthrough the cell membrane
DEPT. OF PHYSIOLOGY, GMCM 29

135. The ions primarily responsible for RMP
1.Na
+
2.K
+
3.A
-
A
-
= Large, negatively charged (anionic) intracellular proteins
DEPT. OF PHYSIOLOGY, GMCM 30

136. FACTORS involved
in Genesis of RMP 5
DEPT. OF PHYSIOLOGY, GMCM 31

137. “Thephenomenonofpredictableandunequal
distributionofpermeantchargedionsoneither
sideofasemipermeablemembrane,inthepresence
ofimpermeantchargedions”
1. The Gibbs-Donnaneffect
DEPT. OF PHYSIOLOGY, GMCM 33

138. DEPT. OF PHYSIOLOGY, GMCM 34

139. DEPT. OF PHYSIOLOGY, GMCM 36
Non
permeable
anion

140. DEPT. OF PHYSIOLOGY, GMCM 38

141. DEPT. OF PHYSIOLOGY, GMCM 39

142. DEPT. OF PHYSIOLOGY, GMCM 40

143. “Thephenomenonofpredictableandunequal
distributionofpermeantchargedionsoneither
sideofasemipermeablemembrane,inthepresence
ofimpermeantchargedions”
The Gibbs-Donnaneffect
DEPT. OF PHYSIOLOGY, GMCM 41

144. When 2 ionized solutions are separated by a semi-permeable
membrane, at equilibrium
1.Each solution will be electrically neutral
2.(Diffusible cations)
AX (Diffusible anions)
A =
(Diffusible cations)
BX (Diffusible anions)
B
DEPT. OF PHYSIOLOGY, GMCM 43

145. •Diffusible cations (K
+
) more on the side of non-diffusible
anions (proteins) : ICF
•Less diffusible cations (Na
+
) more on the side of diffusible
anions (Cl
-
) : ECF
DEPT. OF PHYSIOLOGY, GMCM 44

146. Na
+
, Cl
-
K
+
K
+
, anions
Na
+
,Cl
-
ECF
ICF
DEPT. OF PHYSIOLOGY, GMCM 45

147. Ions ECF mmol/L ICF mmol/L
Na
+
150 15
K
+
5.5 150
Cl
-
125 9
Proteins 0 65
Distribution of ions
DEPT. OF PHYSIOLOGY, GMCM 46

148. 2. Selective Permeability of the cell membrane
•Separates ECF & ICF
DEPT. OF PHYSIOLOGY, GMCM 47

149. •Cytoplasm has diffusible & non-diffusible ions
•Membrane is freely permeableto K
+
andCl
-
•Moderately permeable toNa
+
•Impermeableto intracellular proteins and organic
phosphates (negatively chargedions)
DEPT. OF PHYSIOLOGY, GMCM 48

150. Permeability to K+
•Potassium sodium leak channels
•About 50-100 times than that for
Na
+
•Hydrated K
+
ion is smaller
DEPT. OF PHYSIOLOGY, GMCM 49

151. •K+ efflux -not compensated by Na influx
•K+ efflux is not accompanied by negatively charged
anions
•More negative ions remain inside the cell → creates
negativityinside the cell
DEPT. OF PHYSIOLOGY, GMCM 50

152. Asymmetric distribution of ions
↓
Concentration & Electrical gradients
↓
Diffusion
DEPT. OF PHYSIOLOGY, GMCM 52

153. K
+
as the only diffusible ion
DEPT. OF PHYSIOLOGY, GMCM 54

154. DEPT. OF PHYSIOLOGY, GMCM 55

155. ECF 5.5 mmol/L of H
2O
ICF 150 mmol/L of H
2O
C
G
E
G
DEPT. OF PHYSIOLOGY, GMCM 56

156. •Equilibrium is reached
•Driving forces down conc. & electrical gradients are
equal and opposite
•No net movement
DEPT. OF PHYSIOLOGY, GMCM 57

157. 3. Nernst Equation
DEPT. OF PHYSIOLOGY, GMCM 59

158. Nernst potential/ Equilibrium potential for K+
E
k= -61.5 log [K
i
+
]= -90mV (37 degC)
[K
o
+
]
[K
o
+
] = K
+
concentration outside the cell
[K
i
+
] = K
+
concentration inside the cell
DEPT. OF PHYSIOLOGY, GMCM 60

159. DEPT. OF PHYSIOLOGY, GMCM 61

160. K
+
as the only diffusible ion
DEPT. OF PHYSIOLOGY, GMCM 62

161. DEPT. OF PHYSIOLOGY, GMCM 63

162. 1.Polarity/ electrical charge
2.Permeability of membrane to each
3.Concentration inside & outside
When multiple ions are involved,
Membrane potential depends on
DEPT. OF PHYSIOLOGY, GMCM 64

163. 4. Goldman Hodgkin –Katz equation
•With this equation RMP calculated is–67 mV
DEPT. OF PHYSIOLOGY, GMCM 65

164. DEPT. OF PHYSIOLOGY, GMCM 66

165. •Greater the permeability of an ion, greater is the tendency
for that ion to drive the membrane potential towards its own
equilibrium potential
DEPT. OF PHYSIOLOGY, GMCM 67

166. 5. Na
+
-K
+
ATPase
•Steady ion leaks cannot continue forever without
eventually dissipating the ion gradients
•This is prevented by the Na
+
-K
+
ATPase
•It actively moves 3 Na
+
out and 2 K
+
in against their
electrochemical gradients
DEPT. OF PHYSIOLOGY, GMCM 69

167. Jens Skou
Nobel Prize in Physiology and Medicine 1997

168. DEPT. OF PHYSIOLOGY, GMCM 71

169. •Results in continuous loss of positive charges from inside
the membrane
•Creates an additional degree of negativity
•So it is electrogenic and contributes to RMP about –4mV
•Helps to maintain osmotic balance.
DEPT. OF PHYSIOLOGY, GMCM 72

170. 1.Donnaneffect & Gibbs DonnanEquilibrium
2.Selective permeability of cell membrane to ions
3.Nernst Equation
4.Goldman Hodgkin Katz Equation
5.Sodium-potassium ATPase pump
Factors involved in genesis of RMP
DEPT. OF PHYSIOLOGY, GMCM 73

171. Factors affecting RMP
1.ECF K
+
concentration
ECF K
+
↑: magnitude of RMP ↓ →neuron becomes more
excitable
2.Inhibition of Na
+
K
+
ATPase
3.ECF Na
+
: no effect
DEPT. OF PHYSIOLOGY, GMCM 74

172. •If the extracellular level of K + is increased (hyperkalemia), the resting
potential moves closer to the threshold for eliciting an action
potential, thus the neuron becomes more excitable.
•If the extracellular level of K + is decreased (hypokalemia), the
membrane potential is reduced and the neuron is hyperpolarized.
DEPT. OF PHYSIOLOGY, GMCM 75

173. NERVE PHYSIOLOGY -4
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM

174. Electrical Properties of a Neuron
1.Excitability
2.Conductivity
DEPT. OF PHYSIOLOGY, GMCM 3

175. Excitability
•Stimulus
•Types
•Strength/ intensity
Threshold stimulus
Subthreshold stimulus
Suprathreshold stimulus
DEPT. OF PHYSIOLOGY, GMCM 4

176. Application of stimulus will produce
1.Local non-propagated potentials
Electrotonic potentials
2.Propagated potentials
Action potential/ nerve impulse
DEPT. OF PHYSIOLOGY, GMCM 5

177. Specific Learning Objectives
•Electrotonic Potential
•Action Potential
•Ionic Basis of Action Potential
•Graded Potential v/s Action Potential

178. ElectrotonicPotentials
ELECTROTONIC
POTENTIALS
DEPT. OF PHYSIOLOGY, GMCM 11

179. •Demonstrated by placing recording electrodes within a
few millimeters of a stimulating electrode
•Applying subthreshold stimuliof fixed duration
DEPT. OF PHYSIOLOGY, GMCM 12
Recording of electrotonic potential

180. Subthreshold
Stimulus

181. •Leads to a localizedpotential change
•Rises sharply and decays exponentially with time
•Graded response can be produced both at cathode and
anode
1.Catelectrotonicpotential
2.Anelectrotonic potential
DEPT. OF PHYSIOLOGY, GMCM 14

182. DEPT. OF PHYSIOLOGY, GMCM 15

183. DEPT. OF PHYSIOLOGY, GMCM 17

184. Graded Potential –Examples
1.End plate potential
2.Post synaptic potential
3.Generator or receptor potential
DEPT. OF PHYSIOLOGY, GMCM 18

185. Specific Learning Objectives
•Electrotonic Potential
•Action Potential
•Ionic Basis of Action Potential
•Graded Potential v/s Action Potential

186. ACTION
POTENTIAL

187. •Brief, rapid, largedepolarizing changes in membrane
potential
•Transiently, resting negative potential →positive potential
•Conducted, propagated along the nerve fiber
•Non decrementalfashion
•Nerve signals are transmitted by action potentials

188. How is an action potential recorded?
1.Stimulating Electrodes (min -threshold stimuli)
2.Recording Electrodes
3.Amplifier
4.Cathode Ray Oscilloscope

189. Threshold Stimuli

190. 1.Resting stage
2.Depolarization
3.Repolarization
Stages of Action Potential

192. 1.RMP –70mV (polarized state)
2.Stimulus artifact
3.Latent period (Isoelectric potential interval)
4.Depolarization (reverse polarization)
5.Firing level
6.Spike potential
7.After depolarization
8.After hyperpolarization

193. Marked changes in membrane permeability and
ion movement lead to action potential.

194. NERVE PHYSIOLOGY -5
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM

195. Specific Learning Objectives
•Ionic Basis of Action Potential
•Properties of Action Potential
•Graded Potential v/s Action Potential
•Types of Action Potential
DEPT. OF PHYSIOLOGY, GMCM 4

196. IONIC BASIS OF
ACTION POTENTIAL
DEPT. OF PHYSIOLOGY, GMCM 5

197. 1.Stimulus artifact –Current leakage from stimulating
to recording electrodes
2.Latent Period –Time taken by the impulse to travel
along the axon
•Distance between electrodes
•Velocity of conduction
DEPT. OF PHYSIOLOGY, GMCM 6

198. 3. Depolarization
Threshold stimulus
↓
Initial slow depolarization (a change of 7–15mV)
(opening of few voltage gated Na+ channels)
DEPT. OF PHYSIOLOGY, GMCM 7

199. Voltage Gated Sodium Channel
DEPT. OF PHYSIOLOGY, GMCM 8

200. Threshold stimulus
↓
Initial slow depolarization (a change of 7–15mV)
(opening of few voltage gated Na+ channels)
↓
Rapid depolarization(at–55mV) Firing Level
(opening of more and more voltage gated Na+ channels)
DEPT. OF PHYSIOLOGY, GMCM 9

201. Feedback Control in Voltage Gated Ion Channels / Hodgkin Cycle
DEPT. OF PHYSIOLOGY, GMCM 10

202. Firing Level
•At -55mV more Na channels opens →gush of Na
+
into
cell (500 –5000 fold)
DEPT. OF PHYSIOLOGY, GMCM 11

203. •Membrane potential moves towards equilibrium potential
for Na
+
: +61 mV
•But membrane potential does not reach to +61 mV
because Na
+
conductance is short lived.
DEPT. OF PHYSIOLOGY, GMCM 12

204. DEPT. OF PHYSIOLOGY, GMCM 13

205. DEPT. OF PHYSIOLOGY, GMCM 14

206. 1.After few 10,000
th
of a second inactivation gate closed
→Na
+
influx ↓
•Inactivation gate will remain closed till (or near) reaching
RMP again.
4. Repolarization
DEPT. OF PHYSIOLOGY, GMCM 15

207. 2.Direction of electrical gradient of Na
+
is reversed during
overshoot
•Leads todecrease in Na
+
influx
3.Opening of voltage gated K
+
channel also contributes to
repolarization
DEPT. OF PHYSIOLOGY, GMCM 16

208. Voltage Gated Potassium Channel
DEPT. OF PHYSIOLOGY, GMCM 17

209. •Only 1 gate inside, resting state gate is closed
•As membrane potential rises -70 to 0 →slow
conformational changein the K
+
gate occurs →
opening of gate
•So repolarization is due to both ↑ K
+
efflux and ↓ Na+
influx
DEPT. OF PHYSIOLOGY, GMCM 18

210. Feedback Control in Voltage Gated Ion Channels
DEPT. OF PHYSIOLOGY, GMCM 19

211. DEPT. OF PHYSIOLOGY, GMCM 20

212. DEPT. OF PHYSIOLOGY, GMCM 21

213. 5.After depolarizationdue to slowing of K
+
efflux
6.After hyperpolarizationdue to slow return of K
+
channel to closed state
DEPT. OF PHYSIOLOGY, GMCM 22

214. 7.Re-establishing Na
+
and K
+
ionic gradients
•Transmissionofactionpotentialslightlyreduces
concentrationdifferencesofNa
+
andK
+
insideand
outsidethemembrane
DEPT. OF PHYSIOLOGY, GMCM 23

215. •Achieved by action of the Na
+
-K
+
pump
•This pump requires energy derived from ATP
•So “recharging” of the nerve fiber is an active
metabolic process.
DEPT. OF PHYSIOLOGY, GMCM 24

216. Jens Skou
Nobel Prize in Physiology and Medicine 1997
DEPT. OF PHYSIOLOGY, GMCM 25

217. •Decrease in ECF calcium increase excitability
•By decreasing the amount of depolarization necessary
for opening of Na
+
channels
•Increase in ECF calcium levels decreases excitability
and stabilizes the membrane
Effect of Ca
2+
on excitability
DEPT. OF PHYSIOLOGY, GMCM 26

218. DEPT. OF PHYSIOLOGY, GMCM 27

219. Specific Learning Objectives
•Ionic Basis of Action Potential
•Properties of Action Potential
•Graded Potential v/s Action Potential
•Types of Action Potential
DEPT. OF PHYSIOLOGY, GMCM 29

220. PROPERTIES OF
ACTION POTENTIAL
30

221. Properties of Action Potential
1.Threshold stimulus
2.All or none response
3.Propagation of action potential
4.Refractory period
DEPT. OF PHYSIOLOGY, GMCM 31

222. •The stimulus that brings the membrane potential to the
firing level (–55 mV) is known as threshold stimulus.
•Threshold stimulus is defined as the lowest strength of
stimulus that elicits an action potential.
1. Threshold Stimulus
DEPT. OF PHYSIOLOGY, GMCM 32

223. Strength Duration Curve
DEPT. OF PHYSIOLOGY, GMCM 35

224. •Rheobase:minimumintensityofstimuluswhich
ifappliedforadequatetime(utilizationtime)
producesaresponse.
•Chronaxie:minimumdurationforwhichstimulus
ofdoubletherheobaseintensitymustbeappliedto
producearesponse
DEPT. OF PHYSIOLOGY, GMCM 36

225. •Within physiological limits, chronaxieof a given excitable tissue
is constant.
•Gives an idea about the excitability of a tissue. The lesser the
chronaxie, greater is the excitability.
•Nerves have a shorter chronaxie compared to muscles.
DEPT. OF PHYSIOLOGY, GMCM 37

226. Slowly rising currents fail to induce an action potential in
the nerve because the nerve undergoes adaptation.
DEPT. OF PHYSIOLOGY, GMCM 38

227. 2. All or None Response
•Actionpotentialfailstooccurifthestimulusis
subthresholdinmagnitude.
•Itoccurswithconstantamplitudeandshape
regardlessofthestrengthofstimulus,ifstimulusisat
orabovethresholdintensity.
DEPT. OF PHYSIOLOGY, GMCM 39

228. DEPT. OF PHYSIOLOGY, GMCM 40

229. 2. All or None Response
•Actionpotentialfailstooccurifthestimulusis
subthresholdinmagnitude
•Itoccurswithconstantamplitudeandshape
regardlessofthestrengthofstimulus,ifstimulusis
atorabovethresholdintensity
Why?
DEPT. OF PHYSIOLOGY, GMCM 41

230. •After the threshold level is achieved, the amount of sodium
influx becomes independent of the stimulus factor.
•The activation gates of voltage-gated Na+ channels open as
soon as -55mV is reached.
DEPT. OF PHYSIOLOGY, GMCM 42

231. 3. Propagation of Action Potential (AP)
•APelicitedatanypointonanexcitablemembrane
excitesadjacentportionsofthemembrane.
•ResultsinpropagationofAPalongmembrane.
DEPT. OF PHYSIOLOGY, GMCM 43

232. 1.Excited portion rapidly develops ↑ permeability to
Na
+
and influx begins
In unmyelinated axon
DEPT. OF PHYSIOLOGY, GMCM 44

233. DEPT. OF PHYSIOLOGY, GMCM 45

234. 2.Positive charges from membrane ahead of and behind
AP flow into area of negativity -Current Sink
3.Charges are carried by inward-diffusing Na
+
ions
through depolarized membrane for several millimeters
in both directions.
DEPT. OF PHYSIOLOGY, GMCM 46

235. DEPT. OF PHYSIOLOGY, GMCM 47

236. 4.Thesepositivechargesincreasethevoltagetolevels
abovethethresholdvoltageforinitiatinganaction
potential
5.SoNa
+
channelsinthesenewareasimmediately
openandtheexplosiveactionpotentialspreads
DEPT. OF PHYSIOLOGY, GMCM 48

237. DEPT. OF PHYSIOLOGY, GMCM 49

238. DEPT. OF PHYSIOLOGY, GMCM 50

239. Saltatoryconduction (Myelinated Axon)
1.Myelinisaneffectiveinsulator,andcurrentflow
throughitisnegligible
2.DepolarizationtravelsfromonenodeofRanvierto
thenext
DEPT. OF PHYSIOLOGY, GMCM 51

240. DEPT. OF PHYSIOLOGY, GMCM 52

241. 3.Currentsinkatactivenodedepolarizenodeaheadof
theactionpotentialtofiringlevel
4.This“jumping”ofdepolarizationfromnodetonode
iscalledsaltatoryconduction
5.Soconductionupto50timesfasterthanthefastest
unmyelinatedfibers
DEPT. OF PHYSIOLOGY, GMCM 53

242. Advantages
1.The velocity of conduction is faster
2.Helps to conserves energy
In unmyelinated axons, voltage-gated channels open throughout
the axonal length causing activation of larger number of Na+-K+
ATPaseand higher expenditure of energy.
DEPT. OF PHYSIOLOGY, GMCM 54

243. DEPT. OF PHYSIOLOGY, GMCM 55

244. 1.Orthodromicconduction
2.Antidromicconduction
DEPT. OF PHYSIOLOGY, GMCM 56

245. •When AP is initiated in the middle of the axon, two
impulses traveling in opposite directions are set up.
•Impulses usually pass in one direction only, i.e., from
synaptic junctions or receptors along axons to their
termination –orthodromic conduction.
DEPT. OF PHYSIOLOGY, GMCM 57

246. •Sincetheimpulseconductedinopposite
direction(antidromic)failstopassthefirst
synapsetheyencounter&dieout.
•Becausesynapsespermitconductiononlyin
onedirection.
DEPT. OF PHYSIOLOGY, GMCM 58

247. DEPT. OF PHYSIOLOGY, GMCM 59

248. NERVE PHYSIOLOGY -5b
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM

249. Specific Learning Objectives
•Ionic Basis of Action Potential
•Properties of Action Potential
•Properties of AP Continued
•Graded Potential v/s Action Potential
•Types of Action Potential
•Velocity of Nerve Conduction
•Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 61DEPT. OF PHYSIOLOGY, GMCM

250. Monophasic action potential
DEPT. OF PHYSIOLOGY, GMCM 63

251. Biphasic action potential
64

252. 4. Refractory period
•AbsoluteRefractory Period
•RelativeRefractory Period
DEPT. OF PHYSIOLOGY, GMCM 65

253. Absolute Refractory Period
•Periodinwhichastimulus,nomatterhowstrong,willnot
beabletoexcitethenerve
•Correspondstotheperiodfromthefiringleveltothe
pointatwhichrepolarizationisaboutone-third
complete.
DEPT. OF PHYSIOLOGY, GMCM 66

254. DEPT. OF PHYSIOLOGY, GMCM 67

255. Basis
1.Shortly after action potential is initiated, Na
+
channels
become inactivated.
2.No amount of excitatory signal will re-open inactivation
gates till membrane potential return to or near the RMP.
DEPT. OF PHYSIOLOGY, GMCM 68

256. DEPT. OF PHYSIOLOGY, GMCM 69

257. DEPT. OF PHYSIOLOGY, GMCM 70

258. Relative Refractory period
•Periodinwhichastimulus,strongerthannormal
stimulicancauseexcitation
•Correspondstotheperiodfromtheone-thirdof
repolarizationtothestartofafter-depolarization
DEPT. OF PHYSIOLOGY, GMCM 71

259. Na
+
channelsreopenwhenmembranepotentialreturns
toorneartheoriginalrestingmembranepotential.
DEPT. OF PHYSIOLOGY, GMCM 72

260. DEPT. OF PHYSIOLOGY, GMCM 74

261. Specific Learning Objectives
•Ionic Basis of Action Potential
•Properties of Action Potential
•Properties of AP Continued
•Graded Potential v/s Action Potential
•Types of Action Potential
•Velocity of Nerve Conduction
•Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 76DEPT. OF PHYSIOLOGY, GMCM

262. Graded Potential v/s Action Potential
DEPT. OF PHYSIOLOGY, GMCM 77

263. Graded potential Action potential
1.No threshold stimuli
needed
2.Amplitudeof potential is
proportionate to the
intensity of stimulus
3.Can get summated
1.A threshold stimuli is
needed
2.Amplitude remains
constanteven if intensity of
stimulus is increased above
threshold stimuli
3.Cannotbe summated
DEPT. OF PHYSIOLOGY, GMCM 78

264. Graded potential Action potential
4.So does not obey “All or
none” law
5.Can be either depolarizing
or hyperpolarizing
6.Change in membrane
potential that is confined to
relatively small region on
membrane
4.Obeys “All or none” law
5.It is always depolarizing
6.Spreadsover a larger area
on the membrane
DEPT. OF PHYSIOLOGY, GMCM 79

265. 7.These potentials cannot be
conducted as impulses –
Non-propagating
potentials
8.NoRefractory period
7.Can be conducted as
impulses –Propagating
potentials
8.Has a Refractory period
Graded potential Action potential
DEPT. OF PHYSIOLOGY, GMCM 80

266. Specific Learning Objectives
•Ionic Basis of Action Potential
•Properties of Action Potential
•Properties of AP Continued
•Graded Potential v/s Action Potential
•Types of Action Potential
•Velocity of Nerve Conduction
•Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 82DEPT. OF PHYSIOLOGY, GMCM

267. Types of Action Potentials
DEPT. OF PHYSIOLOGY, GMCM 83

268. Types of action potential
1.Spikepotential (Nerve & Skeletal muscle)
2.Plateaupotential (Cardiac muscle)
3.Rhythmic type of action potential
DEPT. OF PHYSIOLOGY, GMCM 84

269. Plateau potential
85

270. Rhythmic type of action potential
•Seen in rhythmically discharging cells
•SA node, AV node & conducting system of heart
•Smooth muscles of intestine & some neurons in CNS
•Pacemaker potential or pre-potential
DEPT. OF PHYSIOLOGY, GMCM 86

271. DEPT. OF PHYSIOLOGY, GMCM 87

272. DEPT. OF PHYSIOLOGY, GMCM 90
Specific Learning Objectives
•Ionic Basis of Action Potential
•Properties of Action Potential
•Properties of AP Continued
•Graded Potential v/s Action Potential
•Types of Action Potential
•Velocity of Nerve Conduction
•Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM

273. VelocityofNerve Conduction
DEPT. OF PHYSIOLOGY, GMCM 91

274. Velocity of nerve conduction
Factors that increase velocityFactors that decrease velocity
Diameter Pressure
Myelination Narcotic drugs
Increase in Temperature Decrease in temperature
DEPT. OF PHYSIOLOGY, GMCM 92

275. “highly differentiated functions of single nerve fibers”
ErlangerandGassser
Nobel PrizeinMedicine
or Physiology, 1944
DEPT. OF PHYSIOLOGY, GMCM 93

276. Erlanger Gasser classification of nerve fibers
DEPT. OF PHYSIOLOGY, GMCM 94

277. DEPT. OF PHYSIOLOGY, GMCM 95

278. Numerical classification of sensory nerve fibers
DEPT. OF PHYSIOLOGY, GMCM 96

279. Susceptibility to Hypoxia, Pressure and LAs
DEPT. OF PHYSIOLOGY, GMCM 97

280. DEPT. OF PHYSIOLOGY, GMCM 99
Specific Learning Objectives
•Ionic Basis of Action Potential
•Properties of Action Potential
•Properties of AP Continued
•Graded Potential v/s Action Potential
•Types of Action Potential
•Velocity of Nerve Conduction
•Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM

281. Properties of a Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 100

282. 1.Effect of stimuli with different intensities
•Sub threshold stimulus
•Threshold stimulus
•Maximal stimulus
•Supra maximal stimulus
2.Compound action potential
DEPT. OF PHYSIOLOGY, GMCM 101

283. DEPT. OF PHYSIOLOGY, GMCM 102

284. •Potentialchangesrecordedextracellularlyfrommixednerves
representanalgebraicsummationoftheall-or-noneaction
potentialsofmanyaxons.
DEPT. OF PHYSIOLOGY, GMCM 103

285. •Withsubthresholdstimuli,noresponseoccurs
•Whenthestimuliareofthresholdintensity,axons
withlowthresholdsfireandasmallpotentialchange
isobserved.
DEPT. OF PHYSIOLOGY, GMCM 104
1.Effect of stimuli with different intensities

286. •Astheintensityofthestimulatingcurrentisincreased,
theaxonswithhigherthresholdsarealsostimulated
•Electricalresponseincreasesproportionatelyuntil
stimulusisstrongenoughtoexcitealloftheaxons
inthenerve
DEPT. OF PHYSIOLOGY, GMCM 105

287. •Stimulusthatproducesexcitationofalltheaxonsisthe
maximalstimulus
•Applicationofgreater,supramaximalstimuliproduces
nofurtherincreaseinthepotential
DEPT. OF PHYSIOLOGY, GMCM 106

288. •Inmixednerves,thereistheappearanceofmultiple
peaksintheactionpotential.
•Themultipeakedactionpotentialiscalleda
compoundactionpotential.
DEPT. OF PHYSIOLOGY, GMCM 107
2.Compound action potential

289. DEPT. OF PHYSIOLOGY, GMCM 108

290. •Asynchronousdischargeofthevariousfibers
•Differentconductionvelocities
DEPT. OF PHYSIOLOGY, GMCM 109

291. DEPT. OF PHYSIOLOGY, GMCM 110

292. WBC and Nerve Lecture Feedback (google.com)
DEPT. OF PHYSIOLOGY, GMCM 111

293. [email protected]
DEPT. OF PHYSIOLOGY, GMCM 113

294. DEPT. OF PHYSIOLOGY, GMCM 1
Q

295. Short Essay (8 marks)
1.Explain chronaxie, rheobase, utilizationtime. Draw strength
duration curve.
Write briefly (4 marks)
2.Ionic Basis ofResting membrane potential.
3.Ionic Basis of Action Potential.
4.Absolute RefractoryPeriod.
Q -KUHS Mar 2021, May 2022
Q -KUHS Feb 2022, May 2022
Q -KUHS July 2022
Q -KUHS Feb 2016

296. Physiological Basis (2 marks)
1.Wallerian Degeneration
2.Sodium Potassium pump helps to maintain RMP.
Draw and Label
1.Action Potential in a Nerve
2.Multipolar Neuron
Q -KUHS July 2022
Q -KUHS Jan 2019
Q -KUHS Nov 2020, Sep 2021
Q -KUHS Aug 2015