1. Membrane potentials XIA Qiang, MD & PhD Department of Physiology
Room 518, Block C, Research Building
School of Medicine, Zijingang Campus
Tel: ☆ (Undergraduate school),
(Medical school)

2. OUTLINE Resting potential Graded potential Action potential
Refractory period

3. Electrocardiogram
ECG

4. Electroencephalogram
EEG

5. Electromyogram
EMG

6. Extracellular Recording

7. Intracellular Recording

8. Opposite charges attract each other and
will move toward each other if not separated
by some barrier.

9. Only a very thin shell of charge difference
is needed to establish a membrane potential.

11. Resting membrane potential
A potential difference across the membranes of inactive cells, with the inside of the cell negative relative to the outside of the cell
Ranging from –10 to –100 mV

12. Overshoot refers to
the development of
a charge reversal.
A cell is
“polarized”
because
its interior
is more
negative
than its
exterior.
Repolarization is
movement back
toward the
resting potential.
Depolarization
occurs
when ion
movement
reduces the
charge
imbalance.
Hyperpolarization is
the development of
even more negative
charge inside the cell.

13. unequal ion distribution (chemical gradient) across the membrane
selective membrane permeability (cell membrane is more permeable to K+)
Na+-K+ pump

14. electrochemical balance
chemical driving force
electrochemical balance
electrical driving force

15. K+ equilibrium potential (EK) (37oC)
The Nernst Equation:
K+ equilibrium potential (EK) (37oC)
R=Gas constant
T=Temperature
Z=Valence
F=Faraday’s constant

16. Begin:
K+ in Compartment 2,
Na+ in Compartment 1;
BUT only K+ can move.
Ion movement:
K+ crosses into
Compartment 1;
Na+ stays in
Compartment 1.
buildup of positive charge in Compartment 1 produces an electrical potential that exactly offsets the K+ chemical concentration gradient.
At the potassium
equilibrium potential:

17. Begin:
K+ in Compartment 2,
Na+ in Compartment 1;
BUT only Na+ can move.
Ion movement:
Na+ crosses into
Compartment 2;
but K+ stays in
Compartment 2.
buildup of positive charge in Compartment 2
produces an electrical potential that exactly
offsets the Na+ chemical concentration gradient.
At the sodium
equilibrium potential:

18. Difference between EK and directly measured resting potential
Ek Observed RP
Mammalian skeletal muscle cell mV -90 mV
Frog skeletal muscle cell mV -90 mV
Squid giant axon mV -70 mV

19. Goldman-Hodgkin-Katz equation
The systemic inflammatory response syndrome (SIRS) is a clinical response arising from a nonspecific insult manifested by two or more of the following:
Fever or hypothermia
Tachycardia
Tachypnea
Leukocytosis, leukopenia, or a left-shift (increase in immature neutrophilic leukocytes in the blood)
Recent evidence indicates that hemostatic changes play a significant role in many SIRS-linked disorders.
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med. 2000; 28:S81-2.
Goldman-Hodgkin-Katz equation

20. Role of Na+-K+ pump: Electrogenic Hyperpolarizing
Establishment of resting membrane potential:
Na+/K+ pump establishes concentration gradient
generating a small negative potential; pump
uses up to 40% of the ATP produced by that cell!
The systemic inflammatory response syndrome (SIRS) is a clinical response arising from a nonspecific insult manifested by two or more of the following:
Fever or hypothermia
Tachycardia
Tachypnea
Leukocytosis, leukopenia, or a left-shift (increase in immature neutrophilic leukocytes in the blood)
Recent evidence indicates that hemostatic changes play a significant role in many SIRS-linked disorders.
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med. 2000; 28:S81-2.

21. Origin of the normal resting membrane potential
K+ diffusion potential
Na+ diffusion
Na+-K+ pump

23. Electrotonic Potential

24. Graded potential
Graded potentials are changes in membrane potential that are confined to a relative small region of the plasma membrane

25. The size of a
graded potential
(here, graded
depolarizations)
is proportionate
to the intensity
of the stimulus.

26. Graded potentials can be:. EXCITATORY. or. INHIBITORY
Graded potentials can be: EXCITATORY or INHIBITORY (action potential (action potential
is more likely) is less likely)
The size of a graded potential is proportional to the size of the stimulus.
Graded potentials decay as they move over distance.

27. Graded potentials decay as they move over distance.

28. Graded potentials Not “all-or-none”
(Local response, local excitation, local potential)
Not “all-or-none”
Electrotonic propagation: spreading with decrement
Summation: spatial & temporal

29. Threshold Potential: level of depolarization needed to trigger an action potential (most neurons have a threshold at -50 mV)

30. Excitable cells: a cell in which the membrane response to depolarisations is nonlinear, causing amplification and propagation of the depolarisation (an action potential).
Action potential
Some of the cells (excitable cells) are capable to rapidly reverse their resting membrane potential from negative resting values to slightly positive values. This transient and rapid change in membrane potential is called an action potential

31. Negative after-potential
A typical neuron action potential
Positive
after-potential
Negative after-potential
Spike potential After-potential

32. Ionic basis of action potential

33. (1) Depolarization: Activation of voltage-gated Na+ channel Blocker:
Tetrodotoxin (TTX)

34. Inactivation of Na+ channel Activation of K+ channel
(2) Repolarization:
Inactivation of Na+ channel
Activation of K+ channel
Blocker:
Tetraethylammonium
(TEA)

36. The rapid opening of voltage-gated Na+ channels
explains the rapid-depolarization phase at the
beginning of the action potential.
The slower opening of voltage-gated K+ channels
explains the repolarization and after hyperpolarization
phases that complete the action potential.

39. voltage-gated Na+ channels allows rapid entry of Na+,
An action potential
is an “all-or-none”
sequence of changes
in membrane potential.
The rapid opening of
voltage-gated Na+ channels
allows rapid entry of Na+,
moving membrane potential
closer to the sodium
equilibrium potential (+60 mv)
Action potentials result
from an all-or-none
sequence of changes
in ion permeability
due to the operation
of voltage-gated
Na+ and K + channels.
The slower opening of
voltage-gated K+ channels
allows K+ exit,
moving membrane potential
closer to the potassium
equilibrium potential (-90 mv)

40. Voltage Gated Channels
Click here to play the
Voltage Gated Channels
and Action Potential
Flash Animation

41. Mechanism of the initiation and termination of AP

42. Re-establishing Na+ and K+ gradients after AP
Na+-K+ pump
“Recharging” process

43. Properties of action potential (AP)
Depolarization must exceed threshold value to trigger AP
AP is all-or-none
AP propagates without decrement

46. Nobel Prize in Physiology or Medicine 1963
How to study ?
Nobel Prize in Physiology or Medicine 1963
"for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane"
Eccles Hodgkin Huxley
Voltage Clamp

47. Currents recorded under voltage clamp condition

48. Nobel Prize in Physiology or Medicine 1991
Patch Clamp
Nobel Prize in Physiology or Medicine 1991
"for their discoveries concerning the function of single ion channels in cells"
Erwin Neher Bert Sakmann

50. Conduction of action potential
Continuous propagation in the unmyelinated axon

51. Action Potential Propagation in an Unmyelinated Neuron Flash Animation
Click here to play the
Action Potential Propagation
in an Unmyelinated Neuron
Flash Animation

52. Saltatory propagation in the myelinated axon

53. Saltatorial Conduction: Action potentials jump from one node to the
next as they propagate along a myelinated axon.

54. Action Potential Propagation
Click here to play the
Action Potential Propagation
in Myelinated Neurons
Flash Animation

55. Excitation and Excitability
Excitability: the ability to generate action potentials is known as EXCITABILITY
Excitation and Excitability
To initiate excitation (AP)
Excitable cells
Stimulation
Intensity
Duration
dV/dt

56. Strength-duration Curve

57. Threshold intensity & Threshold stimulus
Four action potentials, each the result of a stimulus strong enough to cause depolarization, are shown in the right half of the figure.

58. Refractory period following an AP:
A refractory period is a period of time during which an organ or cell is incapable of repeating a particular action potential
Refractory period following an AP:
1. Absolute Refractory Period: inactivation of Na+ channel
2. Relative Refractory Period: some Na+ channels open

60. Factors affecting excitability
Resting potential
Threshold
Channel status

61. The propagation of the action potential from the dendritic
to the axon-terminal end is typically one-way because the
absolute refractory period follows along in the “wake”
of the moving action potential.

62. SUMMARY Resting potential: Graded potential K+ diffusion potential
Na+ diffusion
Na+ -K+ pump
Graded potential
Not “all-or-none”
Electrotonic propagation
Spatial and temporal summation

63. Action potential Refractory period
Depolarization: Activation of voltage-gated Na+ channel
Repolarization: Inactivation of Na+ channel, and activation of K+ channel
Refractory period
Absolute refractory period
Relative refractory period

64. THANK YOU FOR YOUR ATTENTION!