Action Potential

1. Action Potential
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC

2. Learning objectives
 Draw and label typical neuron action potential
 Describe the ionic basic of each of the phases
 List the differences between the action potential
and a local potential
 Define refractory period and differentiate between
absolute and relative refractory periods

3. Action Potential
 Nerve signals are transmitted by action
potentials (A.P)
 A.P are rapid changes in the membrane
potentials that spread rapidly along the nerve
fiber membrane.
 A.P begins with a sudden change from normal
resting negative membrane potential to a
positive potential and ends with an almost
equally rapid change back to negative potential.

4. Action Potential
 The duration of nerve action potential is 0.3 ms.
 To conduct the nerve signal, A.P moves along
the nerve fiber until it comes to the fiber end.
 A.P has the following stages
1. Resting stage
2. Depolarization stage
3. Repolarization stage
4. Rectification

5. Threshold stimulus
 Threshold stimulus is required to initiate A.P.
 Minimum strength of stimulus to initiate a response
 A sudden raise in the membrane potential of 15-30
mv is usually required
 Therefore, in a large nerve fiber, membrane
potential should raise from -90 mv to -65 mv to
trigger the A.P
 This level of -65 mv is said to be the threshold for
stimulation

7. Resting stage
 It is the resting membrane potential before tha
action potential begins.
 Membrane is said to be “polarized”
 -90mv negative membrane potential is present
 Membrane is
1. Highly permeable to potassium
2. Slightly permeable to sodium
3. Impermeable to proteins

8. Depolarization stage
 At this stage, membrane suddenly becomes
permeable to sodium ions
 Tremendous number of positively charged sodium
ions diffuse to the interior of axon
 Potential raises rapidly in positive direction
 This process is called depolarization
 In large nerve fibers, great excess of sodium ions
moving to inside causes the membrane potential to
overshoot beyond the zero level nd to become
somewhat positive.

9. Depolarization stage
 In some smaller fibers, as well as in many
central nervous system neurons, the potential
merely approaches the zero level and does not
overshoot the positive side.

10. Repolarization stage
 Within a few ten-thousandths of a second after
the membrane becomes highly permeable to
sodium ions, the sodium channels begin to
close
 The potassium channels open to a greater
degree than normal.
 Rapid diffusion of potassium ions to the
exterior re establish the normal RMP
 This process is called repolarization

11. Rectification
 The return of the ion to its original ionic state is
achieved through the continued action of
sodium-potassium pump.

12. Voltage gated sodium and
potassium channels
 The necessary factor in causing both
depolarization and repolarization of nerve fiber
during the action potential is the voltage gated
sodium channel.
 A voltage gated potassium channel also plays an
important role in increasing the rapidity of
repolarization of the membrane
 These two voltage gated channels are in addition to
potassium leak channels and sodium potassium
pump

13. Voltage gated sodium channel
 It has two gates
 Activation gate- outside of the channel
 Inactivation gate – inside the channel
 This channel has three stages
1. Resting state – During RMP, activation gate closed and
inactivation gate open. Sodium ions entry is prevented
2. Activation state- Both gates open. Sodium diffuses to
interior
3. Inactive stage- Activation gate open and inactivation
gate closed. Sodium ions entry is prevented

14. Voltage gated sodium and potassium
channels

15. Activation of sodium channel
 When the membrane potential becomes less negative
than RMP
 Raising from -90 mv towards zero
 It reaches a voltage somewhere between -70 and -50 mv,
it cause a sudden conformational change in the
activation gate
 Flipping it all the way to open position
 During this activated state, sodium ions can pour
inward through the channel
 Permeability of sodium is increased 500-to-5000 folds

16. inactivation of sodium channel
 The same increase in the voltage that opens the
activation gate, also closes inactivation gate
 The inactivation gate closes in a few ten-
thousandths of a second after the activation gate
opens
 The conformational change that flips the
inactivation gate to the closed state is a slow
process
 Once, inactivation gate close, sodium ions no
longer pour inside of membrane

17. Positive feedback cycle
 Raise in the membrane potential from -90mv to wards
zero level
 Many voltage gated sodium channels begin opening
 Rapid inflow of sodium ions
 Cause further raise in membrane potential
 Opening still more sodium channels
 More streaming of sodium ions to the interior
 Positive feedback cycle continues until all the sodium
channels are opened
 Another fraction of second inactivation gate closes and
potassium chanel opens and terminates A.P

18. inactivation of sodium channel
 At this point, membrane potential begins to
return towards the resting membrane state-
Repolarization
 Inactivation gate will not reopen until the
membrane potential returns to or near the
original resting membrane potential level
 Therefore, it is usually not possible for sodium
channel to open again with out first repolarizing
the nerve fiber

19. Voltage gated potassium channel
 During resting state, this channel is closed
 Potassium ions are prevented to pass through
this channel to exterior
 When the membrane potential raises from -
90mv towards zero
 Conformational opening of the gate
 Increased potassium diffusion to exterior
 There is a slight delay in opening of this
channel (slow channel)

20. Voltage gated potassium channel
 There is a slight delay in opening of this
channel (slow channel)
 It opens exactly when the inactivation gate of
sodium channel closes
 Decreased sodium diffusion to interior and
increased potassium diffusion to exterior
Contributes for repolarization

21. Summary
 Opening of activation gate of voltage gated
sodium channel - Depolarization
 Closure of inactivation gate of voltage gated
sodium channel - Repolarization
 Opening of voltage gated potassium channel -
repolarization

22. Voltage clamp method
 For measuring the effect of voltage on opening and
closing of voltage gated channels
 This research led to Nobel Prizes for the scientists
responsible, Hodgkin and Huxley.
 Two electrodes are inserted into the nerve fiber
 One electrode is used to measure the voltage of
membrane potential
 Another electrode is used to conduct the electrical
current in and out of the axon
 Changing the membrane potential and can observe its
effect on ion channels

23. Voltage clamp method

24. Other methods to study flow of ions
 Another means of studying the flow of ions
through individual type of channels is to block
one type of channel at a time
 Tetrodotoxin – Sodium channel blocker
 Tetraethylammonium – Potassium channel
blocker

25. Summary of the events that cause A.P

26. Summary of events that cause A.P
 The bottom of the figure shows the changes in the
membrane conductance for sodium and potassium
ions
 During RMP, membrane is highly permeable to
potassium and slightly permeable to sodium
 At the onset of A.P, membrane becomes 5000 folds
more permeable to sodium - depolarization
 The inactivation process then closes the sodium
channel within another fraction of a millisecond -
repolarization

27. Summary of events that cause A.P
 The onset of A.P, also triggers opening of voltage gated
potassium channel
 But this is a slow channel
 It opens exactly when the inactivation gate of sodium
channel closes
 Potassium diffuses to exterior- repolarization
 As it is a slow channel, it closes also slowly ( remain
open long time)
 More potassium ions moves out
 Hyperpolarization
 Sodium-potassium pump brought back the RMP

28. Summary of events that cause A.P
 The middle of the figure shows the ratio of sodium
to potassium conductance at each instance during
A.P
 The top portion of the figure is depiction of action
potential itself
 During early phase of A.P, the ratio of sodium to
potassium conductance increases more than 1000
fold
 More sodium ions flows to interior - Depolarization

29. Summary of events that cause A.P
 Then the sodium channel begins to close and
potassium channel begins to open
 The ratio of conductance shifts far in favor of
high potassium conductance and low sodium
conductance
 Very rapid loss of potassium ions to exterior
 A.P returns quickly to its baseline level

30. Role of other ions during A.P
 Two other types of ions must be considered
 Negative anions
 Calcium ions

31. Impermeable anions inside axon
 Inside the axon are many negatively charges ions
 They can not pass through the membrane channels
 Anions of protein molecules and of many organic
phosphate compounds, sulfate compounds and so
forth.
 As these ions can not leave the interior of axon,
any deficit of positive ions inside the membrane,
cause electro negativity inside

32. Calcium ions
 When there is deficit of calcium ions in ECF
 Opening of sodium channels
 Small increase in the membrane potential from its
normal
 Nerve fiber become highly excitable
 Discharge repeatedly without remains in resting
state
 Fall only 50% below normal concentration of
calcium leads to spontaneous discharge in some
peripheral nerves and cause muscle tetany

33. Calcium ions
 Muscle tetany is sometimes lethal
 Because tetanic contractions of respiratory muscle
 Calcium ions bind to the exterior surface of sodium
channel protein molecules
 Positive charges of these calcium channels alter the
electrical state of the sodium channel protein
 Alters the voltage level required to open the sodium
gate

34. Local potentials
 Not all stimuli result in A.P
 Small stimuli may leads to local changes in the
membrane potentials
 These local changes are below the threshold so
they can not trigger A.P
 These small changes in the cell membrane
potential is called local potentials

35. Difference between local potential and A.P
Local potential
1. Sub-threshold
2. Grades- depending on
strength of stimulus
3. Depolarization or hyper
polarization
4. Conducted only short
distance with a reduction in
magnitude of potential
5. Can be summated
Action Potential
1. Threshold or supra-
threshold
2. Fixed amplitude (All or
none law)
3. Always depolarization
4. Conducted over entire cell
membrane
5. Can not be summated

36. Refractory period
 The nerve can not respond to the second stimulus
during much of the A.P and even longer
 This is referred to refractory period of the nerve
 Two types
1. Absolute Refractory Period
2. Relative Refractory Period

37. Difference between absolute and relative refractory
period
Absolute refractory period
1. period during the A.P where the
nerve can not respond to second
stimulus, no matter how strong it
is
2. Duration is whole of
depolarization and about one
third of repolarization
3. A large number of sodium
channels are inactivated and can
not open until the membrane
returns to the resting state
Relative refractory period
1. Period during the A.P, where the
nerve can respond to the second
stimulus, provided it is greater than
threshold strength
2. Reminder of repolarization and
hyperpolarization phases
3. In the initial part of relative refractory
period, some sodium channels are
still inactivated . Throughout the
relative refractory period, potassium
conductance is high, which opposes
depolarization.

38. THANK YOU