Transcript Introduction

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]
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Outline
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Introduction
The Cast of Chemicals
The Movement of Ions
The Ionic Basis of the Resting
Membrane Potential
Review
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Introduction
What we are?
3
Introduction
Example-A Simple Reflex
(BF3.1)
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Introduction
A Simplified Structure
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Introduction
Structure and Function
Cognition and Behavior
The Nervous System
The Neuron
Collection, Distribution
and Integration
Excitation
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Introduction
A Simplified Function
Encoding by Frequency and Pattern
Conduction
Action Potential
Resting Membrane Potential
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Analogy
Introduction
Light or Heat
Conduction
Electricity
Differences
Generator
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The Beauty
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Important Elements
Ions
Bilayer membrane
Differential permeability to ions
Channels and pumps
Differential responses
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The Cast of Chemicals
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Water and Ions
Cations and anions
Monovalient and divalent
+
+
2+
Na , K , Ca , Cl
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The Cast of Chemicals Phospholipid Membrane
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Phospholipid bilayer
Hydrophilic and hydrophobic
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The Cast of Chemicals
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Channel Protein
Ion channels and ion pumps
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The Cast of Chemicals
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Protein
Amino acids and polypeptides
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The Movement of Ions
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Diffusion
Concentration gradient
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The Movement of Ions
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Electrical Current
Ohm’s law: I = gV
g: conductance
I: currect
V: potential
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The Movement of Ions
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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
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The difference occurs only at
the inside and outside surface.
Vm – Eion = ionic driving
force
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Resting Membrane Potential Equilibrium Potential
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+
Another example: Na
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Resting Membrane Potential Equilibrium Potential
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The Nernst equation
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Resting Membrane Potential
Ionic Distributions
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Resting Membrane Potential
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Ionic Distributions
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Role of Na -K pump – an electrogenic pump
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Resting Membrane Potential
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Ionic Distributions
2+
Role of Ca pump
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Resting Membrane Potential
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Ionic Permeabilities
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Na and K - equilibrium potential
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PNa < 40 X PK
The Goldman equation
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Resting Membrane Potential
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Potassium Channels
Structure
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Resting Membrane Potential
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Potassium Channels
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Effect of external K concentration
Deporlarization
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Resting Membrane Potential
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Potassium Channels
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Protection by blood-brain barrier
Protection by astrocytes via spatial buffering
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Resting Membrane Potential
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Sodium Channels
+
Effect of external Na concentration
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Review
Resting Membrane Potential
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What two functions do proteins in the neuronal
membrane perform to establish and maintain
the resting membrane potential?
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On which side of the neuronal membrane are
Na+ ions more abundant?
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When the membrane is at the K equilibrium
potential, in which direction (in or out) is there
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a net movement of K ?
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Resting Membrane Potential
Review
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There is a much greater K +concentration inside
the cell than outside. Why, then , is the resting
membrane potential negative?
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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]
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Outline
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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
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Introduction
Action Potential
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Action potential vs. electricity
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Electrical charge of ions vs. generator
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Non-degraded vs. degraded conduction
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All-or-none vs. adjustable characteristic
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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
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Generation
Concept of threshold
Concept of all-or-none
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AP-Properties
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Generation
Absolute refractory period
Relative refractory period
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AP-in Theory
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Current and Conductance
A simplified model at resting state (0 - 80 mV)
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AP-in Theory
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Current and Conductance
A simplified model - upon stimulation (-80 – 62 mV)
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AP-in Theory
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Current and Conductance
A simplified model upon stimulation (62 - -80 mV)
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AP-in Reality
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Voltage-Gated Na Channel
Structure – 4 domains
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AP-in Reality
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Voltage-Gated Na Channel
Structure – 6 helices for each domain
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AP-in Reality
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Voltage-Gated Na Channel
Structure – domains for specificities
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AP-in Reality
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Voltage-Gated Na Channel
Depolarization and pore opening
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AP-in Reality
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Voltage-Gated Na Channel
Pore selectivity
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AP-in Reality
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Voltage-Gated Na Channel
Patch-clamp technique
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AP-in Reality
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Voltage-Gated Na Channel
Functional properties
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AP-in Reality
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Voltage-Gated Na Channel
Functional properties
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AP-in Reality
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Voltage-Gated Na Channel
Characteristics
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Open with little delay.
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Stay open for only 1 ms and then close
(inactivate).
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Cannot be opened again by depolarization until
the membrane potential returns to a negative
value near threshold.
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The overshoot is limited by inactivation.
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AP-in Reality
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Voltage-Gated Na Channel
Reminders
 Opining a single channel does not result in
action potential.
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The membrane of axon contains thousands of
Na + channel per m2.
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Concerted action within 1 ms explains the
rapidly rising phase of action potential.
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Inactivation of Na+ channel accounts for the
absolute refractory period.
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AP-in Reality
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Voltage-Gated Na Channel
Toxins
 Effect of TTX and Saxitoxin – channel blocker
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AP-in Reality
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Voltage-Gated Na Channel
Toxins
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Batrachotoxin (Frog) – lower the threshold and
stay open
Toxins from Lilies and Buttercups
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AP-in Reality
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Voltage-Gated K Channel
Repolarization
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Inactivation of Na+ channels (the 1st factor)
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A transient increase in K conductance
Also open in response to depolarization with 1 ms
delay - delay rectifiers (the 2nd factor)
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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
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Orthodromic conduction (10 m/s)
Mechanism of all-or-none
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AP Conduction
Propagation
Characteristics
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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
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Myelin and Saltatory Conduction
Insulation by myelin
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AP Conduction
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Myelin and Saltatory Conduction
Break of insulation for ionic currents to generate AP
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AP, Axons and Dendrites
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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
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Define membrane potential, Na+ equilibrium
potential. Which of these, if any, changes during
the course of an action potential?
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What ions carry the early inward and late outward
currents during the action potential?
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Why is the action potential referred to as “all-ornone”?
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Review
Action Potential
+
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Some voltage-gated K are known as delay
rectifiers. What would happen if these channels
took much longer than normal to open?
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What parts of the cell would you see the labeling of
TTX? What would be the consequence?
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How does action potential conduction velocity vary
with axonal diameter? Why?
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