1. Action
Potentials
David S. Weiss, Ph.D.

2. Measurement of the Action Potential
0 mV + -
-70 mV

3. Membrane potential (mV) Increasing stimulus strength
Nomenclature
Membrane potential (mV)
Subthreshold
response
Hyperpolarizing
afterpotential
Threshold
-70
msec
Stimulating
current
Increasing stimulus strength

4. Milestones •Herman (1870s): Electrical self stimulation.
• Ringer (1880s): Importance of sodium in the
action potential.
• Bernstein (1900): Membrane ‘breakdown’
hypothesis.
• Curtis and Cole: (1940s): Invented the Voltage
clamp.
• Hodgkin and Huxley (1950s): Elucidation of
the ionic basis of the action potential.

5. Bernstein was right!!!! Nitella
Change in
conductance
Action potential
Action potential is accompanied by an increase
in conductance.

6. Decreasing [Na]o decreases amplitude of
Ringer was right!!!!
33% Na
50% Na
Decreasing [Na]o decreases amplitude of
the action potential.

7. Membrane potential (mV) Increasing stimulus strength
Measurement of the overshoot
+50
Overshoot
Membrane potential (mV)
-70
msec
Stimulating
current
Increasing stimulus strength

8. Two Major Developments
Squid giant
axon
Two-electrode
voltage clamp

9. Voltage Clamp Vc Vo - + V Vi I I V
-70
Voltage
Kenneth Cole

10. Alan Hodgkin
Andrew Huxley

11. Hyperpolarization Em Im Depolarization Em Outward current Im
-65 mV Em
-130 mV Im
Depolarization
0 mV Em
-65 mV
Outward current Im
Inward current

12. H-H Assumptions 1) Ions move independently and passively down their
electrochemical gradients. (Nernst stuff)
2) If permeant ions are substituted with non-permeant ions,
then that component of the current should be abolished.

13. Voltage 90 70 50 30 10
Current
-10
-30
Time (msec)

14. Current-Voltage Relationship
-50
+50
100 V

15. Separation of Na and K CurrentsIm
INa
Difference current Vm
Time (ms)

16. Separation of the Na and K CurrentsIK
INa+IK
INa
(msec)

17. Since we can separate the sodium and potassium currents:
We can calculate the sodium and potassium conductances
using ohms law (V=IR):
10% Na
100% Na
Difference

18. Na and K Conductances 0 mV Rest Time (msec) Release of voltage clamp
Membrane
potential
Rest
conductance
Sodium
conductance
Potassium
Time (msec)

19. Conductances at different voltages
Sodium Potassium
44 mV
23 mV
-2 mV
-27 mV
-39 mV
Relative conductance
Voltage
Conductance is voltage dependent and saturates.

20. What is going on I V Voltage Reversed Na current Relative conductance
Relative conductance
Reversed Na
current
-50
+50
100 V
Increasing Na
current
Decreasing Na
current

21. The sodium conductance inactivates
Release of voltage clamp
0 mV
Membrane
potential
Rest
conductance
Sodium
conductance
Potassium
Time (msec)

22. C O I Sodium Conductance Inactivation 1.0 Recovery 0 5 10 15 ms
Pulse 1 Pulse 2
0.5 ms C O
3 ms
7.5 ms
12.5 ms I
1.0
Recovery ms

23. Vm gNa gK Time Course of Conductances and the Action Potential
msec

24. Shape of the Action Potential
Decreasing gNa
Increasing gNa
Inactivating gNa gK
Residual gK

25. Absolute Refractory PeriodV I V I

26. WHY? Absolute Refractory Period
No matter how much you increase the stimulus
intensity…..
you do not get an action potential.
WHY?
Too many sodium channels are inactivated!!

27. Relative Refractory Period

28. WHY? Relative Refractory Period
You must increase the stimulus
intensity…..
...in order get an action potential.
WHY?
Some sodium channels are inactivated and ther is an increased potassium conductance!!

29. Accomodation C O I

30. Hodgkin and Huxley Formulations
Potassium
Sodium
IK=gK (Em-EK)
INa=gNa (Em-ENa)
gK=gK n4
gNa=gNa m3h dn dm dh
=an(1-n)-bnn
=am(1-m)-bmm
=ah(1-h)-bhh dt dt dt
closed
closed
open
inactivated
open

31. Pharmacological Isolation of the Sodium Current
Control
+ tetrodotoxin (TTX)
Tetrodotoxin is a sodium channel blocker isolated from Puffer fish.

32. Pharmacological Isolation of the Sodium Current
Control
+ tetraethylammonium (TEA)

33. All action potentials are not the same
Motoneuron Skeletal muscle Cardiac ventricle
2 msec
5 msec
200 msec

34. Action
Potential
Propagation

35. Spread of a depolarization:
Depolarized
region

36. Saltatory Conduction

37. Ion channels are strongly localized
NaV
Channels
Schwann cell 1
Schwann cell 2
axon
Internode
Node of
Ranvier KV
channels
(Rasband & Shrager, 2000)

38. myelination increases the speed of conduction by a factor of
In general:
myelination increases the speed
of conduction by a factor of
100.

39. Something else that contributes:
Internode:
20 Na channels
per µm2
Node:
10,000 Na channels
per µm2

40. Action potential jumps from node to node
Saltatory Conduction
Action potential jumps from node to node

41. Rate in m/sec = 6x the diameter in µm.
Hursh Factor*
Rate in m/sec = 6x the diameter in µm.
20 µm…………120 m/sec
1 µm ………….6 m/sec
*for myelinated axons

42. Testing the speed of axonal conduction

43. Multiple Sclerosis • Autoimmune • Attacks myelin
The most common early symptoms of MS include:
-Tingling
-Numbness
-Loss of balance
-Weakness in one or more limbs
-Blurred or double vision