1. Neuroscience Chapter 3: The Neuronal Membrane at Rest 高毓儒
Institute of Physiology, School of Medicine
National Yang-Ming University

2. Outline
Introduction
The Cast of Chemicals
The Movement of Ions
The Ionic Basis of the Resting
Membrane Potential
Review

3. What we are?
Introduction

4. Example-A Simple Reflex
Introduction
(BF3.1)

5. A Simplified Structure
Introduction

6. Structure and Function
Introduction
Cognition and Behavior
The Nervous System
Collection, Distribution and Integration
The Neuron
Excitation

7. Encoding by Frequency and Pattern
A Simplified Function
Introduction
Encoding by Frequency and Pattern
Conduction
Action Potential
Resting Membrane Potential

8. Introduction Light or Heat Conduction Electricity Generator Analogy
Differences

9. Differential permeability to ions Channels and pumps
Important Elements
The Beauty
Ions
Bilayer membrane
Differential permeability to ions
Channels and pumps
Differential responses

10. Monovalient and divalent Na , K , Ca , Cl
Water and Ions
The Cast of Chemicals
Cations and anions
Monovalient and divalent
Na , K , Ca , Cl + + 2+ -

11. Phospholipid Membrane
The Cast of Chemicals
Phospholipid bilayer
Hydrophilic and hydrophobic

12. Ion channels and ion pumps
Channel Protein
The Cast of Chemicals
Ion channels and ion pumps

13. Amino acids and polypeptides
Protein
The Cast of Chemicals
Amino acids and polypeptides

14. Concentration gradient
Diffusion
The Movement of Ions
Concentration gradient

15. The Movement of Ions Ohm’s law: I = gV g: conductance I: currect
Electrical Current
The Movement of Ions
Ohm’s law: I = gV
g: conductance
I: currect
V: potential

16. Electrical Current
The Movement of Ions
g = 0
g > 0

17. Resting Membrane Potential
Measurement
Resting Membrane Potential

18. Equilibrium Potential Resting Membrane Potential

19. Equilibrium Potential Resting Membrane Potential
Minuscule changes in ionic concentration
100 mM mM
Large changes in membrane potential
0 mV mV

20. Equilibrium Potential Resting Membrane Potential
The difference occurs only at
the inside and outside surface.
Vm – Eion = ionic driving
force

21. Equilibrium Potential Resting Membrane Potential+
Another example: Na

22. Equilibrium Potential Resting Membrane Potential
The Nernst equation

23. Resting Membrane Potential
Ionic Distributions
Resting Membrane Potential

24. Resting Membrane Potential
Ionic Distributions
Resting Membrane Potential + +
Role of Na -K pump – an electrogenic pump

25. Resting Membrane Potential
Ionic Distributions
Resting Membrane Potential 2+
Role of Ca pump

26. Resting Membrane Potential
Ionic Permeabilities
Resting Membrane Potential + +
Na and K - equilibrium potential
PNa < 40 X PK
The Goldman equation + +

27. Resting Membrane Potential
Potassium Channels
Resting Membrane Potential
Structure

28. Resting Membrane Potential
Potassium Channels
Resting Membrane Potential +
Effect of external K concentration
Deporlarization

29. Resting Membrane Potential
Potassium Channels
Resting Membrane Potential +
Protection by blood-brain barrier
Protection by astrocytes via spatial buffering

30. Resting Membrane Potential
Sodium Channels
Resting Membrane Potential +
Effect of external Na concentration

31. Resting Membrane Potential
Review
Resting Membrane Potential
What two functions do proteins in the neuronal membrane perform to establish and maintain the resting membrane potential?
On which side of the neuronal membrane are Na ions more abundant?
When the membrane is at the K equilibrium potential, in which direction (in or out) is there a net movement of K ? + + +

32. Resting Membrane Potential
Review
Resting Membrane Potential
There is a much greater K concentration inside the cell than outside. Why, then , is the resting membrane potential negative?
When the brain is deprived of oxygen, the mitochondia within neurons cease producing ATP. What effect would this have on the resting membrane potential? +

33. Neuroscience Chapter 4: The Action Potential 高毓儒
Institute of Physiology, School of Medicine
National Yang-Ming University

34. Outline
Introduction
Properties of the action potential
The action potential – in theory
The action potential – in reality
Action potential conduction
Action potential, axons, and dendrites
Review

35. Action potential vs. electricity
Introduction
Action potential vs. electricity
Electrical charge of ions vs. generator
Non-degraded vs. degraded conduction
All-or-none vs. adjustable characteristic
Encoding by frequency and pattern vs. magnitude of electrical power

36. Measurement
AP-Properties

37. The Up and Down
AP-Properties

38. Generation
AP-Properties

39. Generation
AP-Properties
Concept of threshold
Concept of all-or-none

40. AP-Properties Generation Absolute refractory period
Relative refractory period

41. Current and Conductance
AP-in Theory
A simplified model at resting state ( mV)

42. Current and Conductance
AP-in Theory
A simplified model - upon stimulation (-80 – 62 mV)

43. Current and Conductance
AP-in Theory
A simplified model upon stimulation ( mV)

44. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Structure – 4 domains

45. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Structure – 6 helices for each domain

46. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Structure – domains for specificities

47. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Depolarization and pore opening

48. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Pore selectivity

49. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Patch-clamp technique

50. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Functional properties

51. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Functional properties

52. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Characteristics
Open with little delay.
Stay open for only 1 ms and then close (inactivate).
Cannot be opened again by depolarization until the membrane potential returns to a negative value near threshold.
The overshoot is limited by inactivation.

53. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Reminders
Opining a single channel does not result in action potential.
The membrane of axon contains thousands of Na channel per m .
Concerted action within 1 ms explains the rapidly rising phase of action potential.
Inactivation of Na channel accounts for the absolute refractory period. + 2 +

54. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Toxins
Effect of TTX and Saxitoxin – channel blocker

55. Voltage-Gated Na Channel+
Voltage-Gated Na Channel
AP-in Reality
Toxins
Batrachotoxin (Frog) – lower the threshold and stay open
Toxins from Lilies and Buttercups

56. Voltage-Gated K Channel+
Voltage-Gated K Channel
AP-in Reality
Repolarization +
Inactivation of Na channels (the 1st factor)
A transient increase in K conductance
Also open in response to depolarization with 1 ms delay - delay rectifiers (the 2nd factor)
Na -K pump working in the background at all time (the 3rd factor) + + +

57. Overall Changes in Ionic Currents
AP-in Reality

58. Overall Changes in Ionic Currents
AP-in Reality

59. Overall Changes in Ionic Currents
AP-in Reality

60. AP Conduction Propagation Characteristics
Orthodromic conduction (10 m/s)
Mechanism of all-or-none

61. AP Conduction Propagation Characteristics
Only one direction and no turning back
Influenced by axonal size and number of voltage-gated channels
Axonal excitability
Local anesthetics

62. Myelin and Saltatory Conduction
AP Conduction
Insulation by myelin

63. Myelin and Saltatory Conduction
AP Conduction
Break of insulation for ionic currents to generate AP

64. AP, Axons and Dendrites Difference
The membrane of dendrites and cell bodies do not have enough voltage-gated sodium channels.
They do not generate AP.
The spike-initiation zone (axonal hillock) fires the first AP.

65. Difference
AP, Axons and Dendrites

66. Action Potential Review+
Define membrane potential, Na equilibrium potential. Which of these, if any, changes during the course of an action potential?
What ions carry the early inward and late outward currents during the action potential?
Why is the action potential referred to as “all-or- none”?

67. Action Potential Review+
Some voltage-gated K are known as delay rectifiers. What would happen if these channels took much longer than normal to open?
What parts of the cell would you see the labeling of TTX? What would be the consequence?
How does action potential conduction velocity vary with axonal diameter? Why?