lecture 3 dl.ppt
TRANSCRIPT
• Lecture 3
• Voltage-gated channels & the Action Potential
• Channelopathies
Learning Objectives
1. Describe the ion substitution experiments performed by Hodgkin and Huxley in elucidating the ion responsible for the biphasic currents obtained in their voltage clamp experiments with the squid giant axon. What pharmacological agents can also distinguish between these currents?
2. Know how to plot and explain the current-voltage relationship of voltage-gated K+ and Na+ currents.
3. Contrast the topology of various voltage-gated channels and discuss their distinguishing structural feature involved in voltage sensitivity.
4. Know how is voltage dependence recognized in single-channel records obtained from voltage steps to different potentials.
5. Predict the result of an ensemble average of many single-channel current records in response to steps to a particular voltage.
6. Plot the probability of Na+ channel opening and the Na+ current obtained as a function of voltage.
7. Describe an action potential in terms of its dependence on the time course of gNa and gK.
8. Discuss the mechanism of Na+ channel inactivation and its control of the refractory period for generation of multiple action potentials.
9. Describe the events taking place in the neuromuscular junction leading to an action potential.
10. Physiologic Principles Underlying Ion Channelopathies11. Examples of ion channel dysfunction leading to disease (The TRP channel
family and CFTR)
The depolarization-induced biphasic current of squid giant axons
Inward sodium and outward currents
Sodium and Potassium whole-cell currents
Topology of a voltage-gated K+ channel
Ion channel topologies
Voltage-gated channels show an increased Po at more depolarized potentials
Non-inactivating K+ channel currents
Inactivating Na+ channel currents
Po of voltage-gated Na+ channels and the resting K+ conductance
Effect of K+ or Na+ channel activation on membrane potential
Mechanism of fast inactivation of voltage-gated channels
The Action Potential (AP) of a Squid Giant Axon
The neuromuscular junction
Signaling in the neuromuscular junction
Atomic Resolution StructuresVoltage-dependent gating
Long SB, Campbell EB, Mackinnon R. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science. 2005;309:897-903
Channelopathies