Neuroscience
Chapter 3: The Neuronal Membrane at Rest
高毓儒
Institute of Physiology, School of Medicine
National Yang-Ming University
2826-7086 yrkou@ym.edu.tw
1
Outline





Introduction
The Cast of Chemicals
The Movement of Ions
The Ionic Basis of the Resting
Membrane Potential
Review
2
Introduction
What we are?
3
Introduction
Example-A Simple Reflex
(BF3.1)
4
Introduction
A Simplified Structure
5
Introduction
Structure and Function
Cognition and Behavior
The Nervous System
The Neuron
Collection, Distribution
and Integration
Excitation
6
Introduction
A Simplified Function
Encoding by Frequency and Pattern
Conduction
Action Potential
Resting Membrane Potential
7
Analogy
Introduction
Light or Heat
Conduction
Electricity
Differences
Generator
8
The Beauty





Important Elements
Ions
Bilayer membrane
Differential permeability to ions
Channels and pumps
Differential responses
9
The Cast of Chemicals



Water and Ions
Cations and anions
Monovalient and divalent
+
+
2+
Na , K , Ca , Cl
10
The Cast of Chemicals Phospholipid Membrane


Phospholipid bilayer
Hydrophilic and hydrophobic
11
The Cast of Chemicals

Channel Protein
Ion channels and ion pumps
12
The Cast of Chemicals

Protein
Amino acids and polypeptides
13
The Movement of Ions

Diffusion
Concentration gradient
14
The Movement of Ions




Electrical Current
Ohm’s law: I = gV
g: conductance
I: currect
V: potential
15
The Movement of Ions


Electrical Current
g=0
g>0
16
Resting Membrane Potential
Measurement
17
Resting Membrane Potential Equilibrium Potential
18
Resting Membrane Potential Equilibrium Potential
Minuscule changes in ionic concentration
100 mM
99.99999 mM
Large changes in membrane potential
0 mV
80 mV
19
Resting Membrane Potential Equilibrium Potential


The difference occurs only at
the inside and outside surface.
Vm – Eion = ionic driving
force
20
Resting Membrane Potential Equilibrium Potential

+
Another example: Na
21
Resting Membrane Potential Equilibrium Potential

The Nernst equation
22
Resting Membrane Potential
Ionic Distributions
23
Resting Membrane Potential

+
Ionic Distributions
+
Role of Na -K pump – an electrogenic pump
24
Resting Membrane Potential

Ionic Distributions
2+
Role of Ca pump
25
Resting Membrane Potential



+
Ionic Permeabilities
+
Na and K - equilibrium potential
+
+
PNa < 40 X PK
The Goldman equation
26
Resting Membrane Potential

Potassium Channels
Structure
27
Resting Membrane Potential


Potassium Channels
+
Effect of external K concentration
Deporlarization
28
Resting Membrane Potential


Potassium Channels
+
Protection by blood-brain barrier
Protection by astrocytes via spatial buffering
29
Resting Membrane Potential

Sodium Channels
+
Effect of external Na concentration
30
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 ?
31
Resting Membrane Potential
Review

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?
32
Neuroscience
Chapter 4: The Action Potential
高毓儒
Institute of Physiology, School of Medicine
National Yang-Ming University
2826-7086 yrkou@ym.edu.tw
33
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
34
Introduction
Action Potential

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
35
AP-Properties
Measurement
36
AP-Properties
The Up and Down
37
AP-Properties
Generation
38
AP-Properties


Generation
Concept of threshold
Concept of all-or-none
39
AP-Properties


Generation
Absolute refractory period
Relative refractory period
40
AP-in Theory

Current and Conductance
A simplified model at resting state (0 - 80 mV)
41
AP-in Theory

Current and Conductance
A simplified model - upon stimulation (-80 – 62 mV)
42
AP-in Theory

Current and Conductance
A simplified model upon stimulation (62 - -80 mV)
43
AP-in Reality

+
Voltage-Gated Na Channel
Structure – 4 domains
44
AP-in Reality

+
Voltage-Gated Na Channel
Structure – 6 helices for each domain
45
AP-in Reality

+
Voltage-Gated Na Channel
Structure – domains for specificities
46
AP-in Reality

+
Voltage-Gated Na Channel
Depolarization and pore opening
47
AP-in Reality

+
Voltage-Gated Na Channel
Pore selectivity
48
AP-in Reality

+
Voltage-Gated Na Channel
Patch-clamp technique
49
AP-in Reality

+
Voltage-Gated Na Channel
Functional properties
50
AP-in Reality

+
Voltage-Gated Na Channel
Functional properties
51
AP-in Reality
+
Voltage-Gated Na Channel
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.
52
AP-in Reality
+
Voltage-Gated Na Channel
Reminders
 Opining a single channel does not result in
action potential.

The membrane of axon contains thousands of
Na + channel per m2.

Concerted action within 1 ms explains the
rapidly rising phase of action potential.

Inactivation of Na+ channel accounts for the
absolute refractory period.
53
AP-in Reality
+
Voltage-Gated Na Channel
Toxins
 Effect of TTX and Saxitoxin – channel blocker
54
AP-in Reality
+
Voltage-Gated Na Channel
Toxins


Batrachotoxin (Frog) – lower the threshold and
stay open
Toxins from Lilies and Buttercups
55
AP-in Reality
+
Voltage-Gated K Channel
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)
56
AP-in Reality
Overall Changes in Ionic Currents
57
AP-in Reality
Overall Changes in Ionic Currents
58
AP-in Reality
Overall Changes in Ionic Currents
59
AP Conduction
Propagation
Characteristics


Orthodromic conduction (10 m/s)
Mechanism of all-or-none
60
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
61
AP Conduction

Myelin and Saltatory Conduction
Insulation by myelin
62
AP Conduction

Myelin and Saltatory Conduction
Break of insulation for ionic currents to generate AP
63
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.
64
AP, Axons and Dendrites
Difference
65
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-ornone”?
66
Review
Action Potential
+

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?
67