This document discusses excitable tissues and their resting membrane potential and action potentials. It begins by defining excitable tissues as those capable of generating and transmitting electrochemical impulses along their membranes, such as nerves and muscles. It then explains that excitable tissues maintain a more negative resting membrane potential than non-excitable tissues due to ion distributions and gradients established by ion pumps and channels. When an excitable cell is stimulated past its threshold, voltage-gated sodium channels open, allowing sodium to rush in and depolarize the membrane. This triggers voltage-gated potassium channels to then repolarize the membrane, before the sodium-potassium pump restores ion gradients. This process propagates as an action potential along the

1. Excitable Tissues,
Resting Membrane
Potential & Action
Potential
Prof. Vajira Weerasinghe
Professor of Physiology
Department of Physiology
Faculty of Medicine
www.slideshare.net/vajira54

2. Objectives
1. Explain why some membranes are excitable
2. Describe the electrochemical basis of resting
membrane potential
3. Describe the mechanism of generation and
propagation of action potential
4. Explain the differences in action potentials of
skeletal, smooth and cardiac muscles

3. Excitable Tissues
• Tissues which are capable of generation and
transmission of electrochemical impulses along
the membrane
Nerve

4. Excitable tissues
excitable Non-excitable
Red cell
GIT
neuron
muscle
•RBC
•Intestinal cells
•Fibroblasts
•Adipocytes
•Nerve
•Muscle
•Skeletal
•Cardiac
•Smooth

5. Membrane potential
• A potential difference exists across all cell
membranes
• This is called
– Resting Membrane Potential (RMP)

6. Membrane potential
– Inside is negative with respect to the outside
– This is measured using microelectrodes and
oscilloscope
– This is about -70 to -90 mV

7. Excitable tissues
• Excitable tissues have more
negative RMP
( - 70 mV to - 90 mV)
excitable Non-excitable
Red cell
GIT
neuron
muscle
• Non-excitable tissues
have less negative RMP
-53 mV epithelial cells
-8.4 mV RBC
-20 to -30 mV fibroblasts
-58 mV adipocytes

8. Resting Membrane Potential
• This depends on following factors
– Ionic distribution across the membrane
– Membrane permeability
– Other factors
• Na+
/K+
pump

9. Ionic distribution
• Major ions
– Extracellular ions
• Sodium, Chloride
– Intracellular ions
• Potassium, Proteinate
K+
Pr-
Na+
Cl-

10. Ionic distribution
Ion Intracellular Extracellular
Na+
10 142
K+
140 4
Cl-
4 103
Ca2+
0 2.4
HCO3
-
10 28

11. Gibbs Donnan Equilibrium
• When two solutions
containing ions are
separated by membrane
that is permeable to some
of the ions and not to others
an electrochemical
equilibrium is established
• Electrical and chemical
energies on either side of
the membrane are equal
and opposite to each other

12. Flow of Potassium
• Potassium concentration intracellular is more
• Membrane is freely permeable to K+
• There is an efflux of K+
K+
K+K+
K+
K+ K+
K+
K+
K+
K+

13. Flow of Potassium
• Entry of positive ions in to the extracellular fluid
creates positivity outside and negativity inside
K+
K+K+
K+
K+ K+
K+
K+
K+
K+

14. Flow of Potassium
• Outside positivity resists efflux of K+
• (since K+
is a positive ion)
• At a certain voltage an equilibrium is reached
and K+
efflux stops
K+
K+K+
K+
K+ K+
K+
K+
K+
K+

15. Nernst potential (Equilibrium potential)
• The potential level across the membrane that
will exactly prevent net diffusion of an ion
• Nernst equation determines this potential

16. Nernst potential (Equilibrium potential)
• The potential level across the membrane that
will exactly prevent net diffusion of an ion
Ion Intracellular Extracellular Nernst
potential
Na+
10 142 +60
K+
140 4 -90
Cl-
4 103 -89
Ca2+
0 2.4 +129
HCO3
-
10 28 -23
(mmol/l)

17. Goldman Equation
• When the membrane is permeable to several ions the
equilibrium potential that develops depends on
– Polarity of each ion
– Membrane permeability
– Ionic conc
• This is calculated using Goldman Equation (or GHK
Equation)
• In the resting state
– K+ permeability is 50-100 times more than that of Na+

18. Ionic channels
• Leaky channels (leak channels)
– Allow free flow of ions
– K+ channels (large number)
– Na+ channels (fewer in number)
– Therefore membrane is more permeable to K+

19. Na/K pump
• Active transport system for Na+-K+
exchange using energy
• It is an electrogenic pump since 3 Na+
efflux coupled with 2 K+ influx
• Net effect of causing negative charge
inside the membrane
3 Na+
2 K+
ATP ADP

20. Factors contributing to RMP
• One of the main factors is K+ efflux (Nernst Potential:
-90mV)
• Contribution of Na+ influx is little (Nernst Potential:
+60mV)
• Na+/K+ pump causes more negativity inside the
membrane
• Negatively charged protein ions remaining inside the
membrane contributes to the negativity
• Net result: -70 to -90 mV inside

21. Electrochemical gradient
• At this electrochemical equilibrium, there is an exact
balance between two opposing forces:
• Chemical driving force = ratio of concentrations on 2
sides of membrane (concentration gradient)
• The concentration gradient that causes K+ to move from inside to
outside taking along positive charge and
• Electrical driving force = potential difference across
membrane
• opposing electrical gradient that increasingly tends to stop K+ from
moving across the membrane
• Equilibrium: when chemical driving force is balanced
by electrical driving force

22. Action potential

23. Action Potential (A.P.)
• When an impulse is generated
– Inside becomes positive
– Causes depolarisation
– Nerve impulses are transmitted as AP

24. Depolarisation
Repolarisation
-70
+30
RMP
Hyperpolarisation

25. Inside of the membrane is
• Negative
– During RMP
• Positive
– When an AP is generated
-70
+30

26. • Initially membrane is slowly depolarised
• Until the threshold level is reached
– (This may be caused by the stimulus)
-70
+30
Threshold level

27. • Then a sudden
change in polarisation
causes sharp
upstroke
(depolarisation) which
goes beyond the zero
level up to +35 mV
-70
+30

28. • Then a sudden
decrease in
polarisation causes
initial sharp down
stroke (repolarisation)
-70
+30

29. • Spike potential
– Sharp upstroke and
downstroke
• Time duration of AP
– 1 msec
-70
+30
1 msec

30. All or none law
• Until the threshold level the potential is graded
• Once the threshold level is reached
– AP is set off and no one can stop it !
– Like a gun

31. All or none law
• The principle that the strength by which a nerve
or muscle fiber responds to a stimulus is not
dependent on the strength of the stimulus
• If the stimulus strength is above threshold, the
nerve or muscle fiber will give a complete
response or otherwise no response at all

32. • Sub-threshold stimulus No action potential
• Threshold stimulus Action potential is
triggered
• Supra-threshold stimulus Action potential is
triggered
• Strength of the stimulus above the threshold is coded
as the frequency of action potentials

33. Physiological basis of AP
• When the threshold level is reached
– Voltage-gated Na+ channels open up
– Since Na+ conc outside is more than the inside
– Na+ influx will occur
– Positive ion coming inside increases the positivity of the
membrane potential and causes depolarisation
-70
+30
outside
inside
Na+
Voltage-gated Na+ channel

34. Physiological basis of AP
– When membrane potential reaches +30, Na+
channels are inactivated
– Then Voltage-gated K+ channels open up
– K+ efflux occurs
– Positive ion leaving the inside causes more negativity inside
the membrane
– Repolarisation occurs
-70
+30
outside
inside
At +30
K+

35. • Depolarisation
– Change of polarity of the membrane
• from -70 to + 30 mV
• Repolarisation
– Reversal of polarity of the membrane
• from +30 to -70 mV
-70
+30
-70
+30

36. Hyperpolarisation
• When reaching the
Resting level rate
slows down
• Can go beyond the
resting level
– Hyperpolarisation
• (membrane becoming
more negative)
-70
+30

37. Role of Na+/K+ pump
• Since Na+ has come in and K+ has gone out
• Membrane has become negative
• But ionic distribution has become unequal
• Na+/K+ pump restores Na+ and K+ conc slowly
– By pumping 3 Na+ ions outward and 2+ K ions
inward

38. VOLTAGE-GATED ION CHANNELS
• Na+ channel
– This has two gates
• Activation and inactivation gates
outside
inside
Activation gate
Inactivation gate

39. • At rest: the activation gate is closed
• At threshold level: activation gate opens
– Na+ influx will occur
– Na+ permeability increases to 500 fold
• when reaching +30, inactivation gate closes
– Na influx stops
• Inactivation gate will not reopen until resting membrane potential is reached
• Na+ channel opens fast
outside
inside
outside
inside
-70 Threshold level +30
Na+ Na+
outside
inside
Na+m gate
h gate

40. Voltage-gated Na+ channel
• There is a voltage
sensor
• Which opens up
activation gate
• Na+ influx occurs
• Membrane becomes
more positive

41. • When Na+ channel opens
• Na+ influx will occur
• Membrane depolarises
• Rising level of voltage causes many channels to open
• This will cause further Na+ influx
• Thus there a positive feedback cycle
• It does not reach Na+ equilibrium potential (+60mV)
• Because Na+ channels inactivates after opening
• Voltage-gated K+ channels open
• This will bring membrane towards K+ equilibrium
potential

42. VOLTAGE-GATED K+ Channel
• K+ channel
– This has only one gate
outside
inside

43. – At rest: K+ channel is closed
– At +30
• K+ channel open up slowly
• This slow activation causes K+ efflux
• This will cause membrane to become more negative
• Repolarisation occurs
outside
inside
outside
inside
-70 At +30
K+ K+
n gate

44. Basis of hyperpolarisation
• After reaching the resting
still slow K+ channels
may remain open:
causing further negativity
of the membrane
• This is known as
hyperpolarisation
-70
+30
outside
inside
K+

45. Summary

46. Animation

47. Refractory Period
• Absolute refractory
period
– During this period nerve
membrane cannot be
excited again
– Because of the closure
of inactivation gate
-70
+30
outside
inside

48. Refractory Period
• Relative refractory
period
– During this period nerve
membrane can be
excited by supra
threshold stimuli
– At the end of
repolarisation phase
inactivation gate opens
and activation gate
closes
– This can be opened by
greater stimuli strength
-70
+30
outside
inside

50. Na+
and K+
concentrations do not change
during an action potential
• Although during an action potential, large changes
take place in the membrane potential as a result of
Na+
entry into the cell and K+
exit from the cell
• Actual Na+
and K+
concentrations inside and outside of
the cell generally do not change
• This is because compared to the total number of Na+
and K+
ions in the intracellular and extracellular
solutions, only a small number moves across the
membrane during the action potential

51. Propagation of action potential
(Basis of nerve conduction)

52. Propagation of AP
• When one area is depolarised
• A potential difference exists between that site
and the adjacent membrane
• A current flow is initiated
• Current flow through this local circuit is
completed by extra cellular fluid

53. Propagation of AP
• This local current flow will cause opening of
voltage-gated Na+ channel in the adjacent
membrane
• Na+ influx will occur
• Membrane is depolarised

54. Propagation of AP
• Then the previous area become repolarised
• This process continue to work
• Resulting in propagation of AP

55. Propagation of AP

56. Propagation of AP

57. Propagation of AP

58. Propagation of AP

59. Propagation of AP

60. Propagation of AP

61. Propagation of AP

62. Propagation of AP

63. Animation

64. AP propagation along myelinated
nerves
• Na+ channels are conc
around nodes
• Therefore depolarisation
mainly occurs at nodes

65. Distribution of Na+ channels
• Number of Na+ channels per
square micrometer of membrane
in mammalian neurons
50 to 75 in the cell body
350 – 500 in the initial
segment
< 25 on the surface
of myelin
2000 – 12,000 at the nodes of
Ranvier
20 – 75 at the axon
terminal

66. AP propagation along myelinated
nerves
• Local current will flow from one node to another
• Thus propagation of action potential and therefore nerve
conduction through myelinated fibres is faster than
unmyelinated fibre
– Conduction velocity of thick myelinated A alpha fibres is
about 70-100 m/s whereas in unmyelinated fibres it is about
1-2 m/s

67. Saltatory conduction
• This fast conduction through myelinated fibres
is called “saltatory conduction”
• Saltatory word means “jumping”
• This serves many purposes
– By causing depolarisation process to jump at long
intervals it increases the conduction velocity
– It conserves energy for the axon because less loss
of ions due to action potential occurring only at the
nodes

70. Animation

71. Na+/K+ pump
• Re-establishment of Na+ & K+ concentration
after action potential
– Na+/K+ Pump is responsible for this
– Energy is consumed
– Turnover rate of Na+/K+ is pump is much slower
than the Na+, K+ diffusion through channels
3 Na+
2 K+
ATP ADP

72. Clinical importance
• Local anaesthetics (eg. procaine) block voltage
gated sodium channels in pain nerve fibres
• Thereby pain signal transmission is blocked

73. Clinical importance
• Demyelinating diseases
– In certain diseases antibodies would form against myelin
and demyelination occurs
– Nerve conduction slows down drastically
• eg. Guillain-Barre Syndrome (a patient suddenly find difficult to walk,
weakness rapidly progress to upper limbs and respiratory difficulty
will also occur)

74. Muscle action potentials
• Skeletal muscle
• Cardiac muscle
• Smooth muscle

75. Skeletal muscle
• Skeletal muscle is supplied by
somatic nerve
• When there is a signal to the
muscle it contracts and relaxes
• Thus there are two events in the
skeletal muscle
– Electrical - action potential
– Mechanical - contraction

76. Muscle contraction
• Excitation - contraction coupling
– Excitation : electrical event
– Contraction : mechanical event
Mechanical event follows electrical event

77. Skeletal muscle
• Electrical event in a skeletal muscle membrane
is exactly similar to nerve action potential
• Same duration = 1 msec
• Same voltage difference = from -70 to +30 mV

78. Cardiac muscle
• Innervated by autonomic nerves (sympathetic
and parasympathetic)
• Similar to skeletal muscle
– Electrical event - action potential
– Mechanical event – muscle contraction
• However cardiac muscle action potential is
completely different to that of skeletal muscle

79. Cardiac muscle action potential
Phases
• 0: depolarisation
• 1: short repolarisation
• 2: plateau phase
• 3: repolarisation
• 4: resting
Duration is about 200 to 300 msec

80. Cardiac muscle action potential
Phases
• 0: depolarisation
(Na+ influx through fast Na+
channels)
• 1: short repolarisation
(K+ efflux through K+
channels, Cl- influx as well)
• 2: plateau phase
(Ca2+ influx through slow
Ca2+ channels)
• 3: repolarisation
(K+ efflux through K+
channels)
• 4: resting

81. Differences
• Prolonged plateau phase
• Due to opening of slow Ca2+ channels
• Which causes Ca2+ influx
• Membrane is not repolarised immediately
• Mechanical event occurs together with the
electrical event
Excitation : electrical event
Contraction : mechanical event

82. Refractory period
• Cardiac muscle refractory period is about 200
msec
• Equal to the period of depolarisation, plateau
phase & part of repolarisation phases
• The reason for this is that the fast sodium
channels are not fully reactivated and therefore
cannot reopen to normal depolarizing stimuli

84. Smooth muscle
• eg. gut wall, bronchi, uterus
• Controlled by nerve supply (autonomic nerves)
or hormonal control

85. Smooth muscle
• Resting membrane potential may be about -55mV
• There are different types of action potentials
• Spikes
– Slow waves - duration 10-50 ms
voltage from -55 to 0 mV
– Plateau waves - similar to cardiac muscles
• Ca2+ influx is more important that Na+ influx

86. Pacemaker cells
• Cardiac – SA node
• Spontaneous action potentials
• RMP = -40 mV

88. Depolarisation
• Activation of nerve membrane
• Membrane potential becomes positive
• Due to influx of Na+ or Ca++

89. Hyperpolarisation
• Inhibition of nerve membrane
• Membrane potential becomes more negative
• Due to efflux of K+ or influx of Cl-

90. Channel blockers
• Tetrodotoxin (TTX) is a naturally-found poison
that inhibits the voltage-gated Na+
channels
• Tetraethyl ammonium (TEA), a quaternary
ammonium cation, is an agent that inhibits the
voltage-gated K+
channels

91. Other substances
• Oubain
– Plant poison which blocks Na+/K+ pump
• Digitalis
– Drug used in cardiac conditions
– blocks Na+/K+ pump

92. Effect of serum hypocalcaemia
• Concentration of calcium in ECF has a
profound effect on voltage level at which Na+
channels activated
• Hypocalcaemia causes hyperexcitability of the
membrane
• When there is a deficit of Ca2+ (50% below
normal) sodium channels open (activated) by a
small increase in the membrane potential from
its normal level
– Ca2+ ions binds to the Na+ channel and alters the
voltage sensor

93. Effect of serum hypocalcaemia
• Therefore membrane becomes hyperexcitable
• Sometimes discharging spontaneously
repetitively
–tetany occurs
• This is the reason for hypocalcaemia causing
tetany

94. Carpopedal spasms

95. Membrane stabilisers
• Membrane stabilisers (these decrease
excitability)
• Increased serum Ca++
– Hypocalcaemia causes membrane instability and
spontaneous activation of nerve membrane
– Reduced Ca level facilitates Na entry
– Spontaneous activation
• Decreased serum K+
• Local anaesthetics
• Acidosis
• Hypoxia

96. Membrane stabilisers
• Membrane destabilisers (these increase
excitability)
•Decreased serum Ca++
•Increased serum K+
•Alkalosis