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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 yrkou@ym.edu.tw. Outline. Introduction Properties of the action potential The action potential – in theory The action potential – in reality
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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 yrkou@ym.edu.tw
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
Action Potential 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
Measurement AP-Properties
The Up and Down AP-Properties
Generation AP-Properties
Generation AP-Properties • Concept of threshold • Concept of all-or-none
Generation AP-Properties • Absolute refractory period • Relative refractory period
Current and Conductance AP-in Theory • A simplified model at resting state (0 - 80 mV)
Current and Conductance AP-in Theory • A simplified model - upon stimulation (-80 – 62 mV)
Current and Conductance AP-in Theory • A simplified model upon stimulation (62 - -80 mV)
+ Voltage-Gated Na Channel AP-in Reality • Structure – 4 domains
+ Voltage-Gated Na Channel AP-in Reality • Structure – 6 helices for each domain
+ Voltage-Gated Na Channel AP-in Reality • Structure – domains for specificities
+ Voltage-Gated Na Channel AP-in Reality • Depolarization and pore opening
+ Voltage-Gated Na Channel AP-in Reality • Pore selectivity
+ Voltage-Gated Na Channel AP-in Reality • Patch-clamp technique
+ Voltage-Gated Na Channel AP-in Reality • Functional properties
+ Voltage-Gated Na Channel AP-in Reality • Functional properties
+ 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.
+ 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 +
+ Voltage-Gated Na Channel AP-in Reality Toxins • Effect of TTX and Saxitoxin – channel blocker
+ Voltage-Gated Na Channel AP-in Reality Toxins • Batrachotoxin (Frog) – lower the threshold and stay open • Toxins from Lilies and Buttercups
+ 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) + + +
Overall Changes in Ionic Currents AP-in Reality
Overall Changes in Ionic Currents AP-in Reality
Overall Changes in Ionic Currents AP-in Reality
Propagation AP Conduction Characteristics • Orthodromic conduction (10 m/s) • Mechanism of all-or-none
Propagation AP Conduction Characteristics • Only one direction and no turning back • Influenced by axonal size and number of voltage-gated channels • Axonal excitability • Local anesthetics
Myelin and Saltatory Conduction AP Conduction • Insulation by myelin
Myelin and Saltatory Conduction AP Conduction • Break of insulation for ionic currents to generate AP
Difference AP, Axons and Dendrites • 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.
Difference AP, Axons and Dendrites
Review Action Potential + • 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”?
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?