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Neuroscience
Chapter 3: The Neuronal Membrane at Rest
高毓儒
Institute of Physiology, School of Medicine
National Yang-Ming University
2826-7086 [email protected]
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
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The Cast of Chemicals Phospholipid Membrane
Phospholipid bilayer
Hydrophilic and hydrophobic
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The Cast of Chemicals
Channel Protein
Ion channels and ion pumps
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The Cast of Chemicals
Protein
Amino acids and polypeptides
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The Movement of Ions
Diffusion
Concentration gradient
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The Movement of Ions
Electrical Current
Ohm’s law: I = gV
g: conductance
I: currect
V: potential
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The Movement of Ions
Electrical Current
g=0
g>0
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Resting Membrane Potential
Measurement
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Resting Membrane Potential Equilibrium Potential
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Resting Membrane Potential Equilibrium Potential
Minuscule changes in ionic concentration
100 mM
99.99999 mM
Large changes in membrane potential
0 mV
80 mV
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Resting Membrane Potential Equilibrium Potential
The difference occurs only at
the inside and outside surface.
Vm – Eion = ionic driving
force
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Resting Membrane Potential Equilibrium Potential
+
Another example: Na
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Resting Membrane Potential Equilibrium Potential
The Nernst equation
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Resting Membrane Potential
Ionic Distributions
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Resting Membrane Potential
+
Ionic Distributions
+
Role of Na -K pump – an electrogenic pump
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Resting Membrane Potential
Ionic Distributions
2+
Role of Ca pump
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Resting Membrane Potential
+
Ionic Permeabilities
+
Na and K - equilibrium potential
+
+
PNa < 40 X PK
The Goldman equation
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Resting Membrane Potential
Potassium Channels
Structure
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Resting Membrane Potential
Potassium Channels
+
Effect of external K concentration
Deporlarization
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Resting Membrane Potential
Potassium Channels
+
Protection by blood-brain barrier
Protection by astrocytes via spatial buffering
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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 ?
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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?
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Neuroscience
Chapter 4: The Action Potential
高毓儒
Institute of Physiology, School of Medicine
National Yang-Ming University
2826-7086 [email protected]
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
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AP-Properties
Measurement
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AP-Properties
The Up and Down
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AP-Properties
Generation
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AP-Properties
Generation
Concept of threshold
Concept of all-or-none
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AP-Properties
Generation
Absolute refractory period
Relative refractory period
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AP-in Theory
Current and Conductance
A simplified model at resting state (0 - 80 mV)
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AP-in Theory
Current and Conductance
A simplified model - upon stimulation (-80 – 62 mV)
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AP-in Theory
Current and Conductance
A simplified model upon stimulation (62 - -80 mV)
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AP-in Reality
+
Voltage-Gated Na Channel
Structure – 4 domains
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AP-in Reality
+
Voltage-Gated Na Channel
Structure – 6 helices for each domain
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AP-in Reality
+
Voltage-Gated Na Channel
Structure – domains for specificities
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AP-in Reality
+
Voltage-Gated Na Channel
Depolarization and pore opening
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AP-in Reality
+
Voltage-Gated Na Channel
Pore selectivity
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AP-in Reality
+
Voltage-Gated Na Channel
Patch-clamp technique
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AP-in Reality
+
Voltage-Gated Na Channel
Functional properties
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AP-in Reality
+
Voltage-Gated Na Channel
Functional properties
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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.
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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.
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AP-in Reality
+
Voltage-Gated Na Channel
Toxins
Effect of TTX and Saxitoxin – channel blocker
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AP-in Reality
+
Voltage-Gated Na Channel
Toxins
Batrachotoxin (Frog) – lower the threshold and
stay open
Toxins from Lilies and Buttercups
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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)
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AP-in Reality
Overall Changes in Ionic Currents
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AP-in Reality
Overall Changes in Ionic Currents
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AP-in Reality
Overall Changes in Ionic Currents
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AP Conduction
Propagation
Characteristics
Orthodromic conduction (10 m/s)
Mechanism of all-or-none
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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
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AP Conduction
Myelin and Saltatory Conduction
Insulation by myelin
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AP Conduction
Myelin and Saltatory Conduction
Break of insulation for ionic currents to generate AP
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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.
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AP, Axons and Dendrites
Difference
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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”?
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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?
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