Voltage-Gated Ion Channels and the
Action Potential

Voltage-Gated Ion Channels and the
Action Potential

	The Action Potential
		Generation
		Conduction
	Voltage-Gated Ion Channels
		Diversity
		Evolutionary Relationships

Electronically Generated Current Counterbalances the Na⁺ Membrane Current

Equivalent Circuit of the Membrane
Connected to the Voltage Clamp

For Large Depolarizations,
 Both I_Na and I_K Are Activated

I_K is Isolated By Blocking I_Na

I_Na is Isolated By Blocking I_K

V_m = the Value of the Na Battery Plus the
Voltage Drop Across g_Na

Calculation of g_Na

g_Na and g_K Have
Two Similarities and Two Differences

Voltage-Gated Na⁺ Channels Have Three States

Total I_Na is a Population Phenomenon

Na⁺ Channels Open in an All-or-None Fashion

The Action Potential is Generated by
Sequential Activation of g_Na and g_K

Negative Feedback Cycle Underlies
Falling Phase of the Action Potential

Local Circuit Flow of Current Contributes to
Action Potential Propagation

Conduction Velocity Can be Increased by
Increased Axon Diameter and by Myelination

Myelin Speeds Up
Action Potential Conduction

Voltage-Gated Ion Channels and the
Action Potential

	The Action Potential
		Generation
		Conduction
	Voltage-Gated Ion Channels
		Diversity
		Evolutionary Relationships

Opening of Na⁺ and K ⁺ Channels is Sufficient to Generate the Action Potential

However, a Typical Neuron Has Several Types of
Voltage-Gated Ion Channels

Functional Properties of Voltage-Gated
Ion Channels Vary Widely

	Selective permeability
	Kinetics of activation
	Voltage range of activation
	Physiological modulators

Voltage-Gated Ion Channels Differ in their
Selective Permeability Properties

Voltage-Gated K⁺ Channels Differ Widely in Their Kinetics of Activation and Inactivation

Voltage-Gated Ca⁺⁺ Channels Differ in Their Voltage Ranges of Activation

The Inward Rectifier K⁺ Channels and HCN Channels Are Activated by Hyperpolarization

Functional properties of Voltage-Gated
Ion Channels Vary Widely

	Selective permeability
	Kinetics of activation
	Voltage range of activation
	Physiological modulators: e.g., phosphorylation, binding of intracellular Ca++ or cyclic nucleotides, etc.

Physiological Modulation

HCN Channels That Are Opened by Hyperpolarization Are Also Modulated by cAMP

Voltage-Gated Ion Channels Belong to
Two Major Gene Superfamilies

Voltage-Gated Ion Channel Gene Superfamilies

The a-Subunits of Voltage-Gated Channels
Have Been Cloned

Voltage-Gated Cation-Permeant Channels Have a Basic Common Structural Motif That is Repeated Four-fold

Four-Fold Symmetry of Voltage-Gated Channels Arises in Two Ways

Slide 35

Voltage-Gated Cation-Permeant Channels Use the Same Structural Elements for Gating and for Ion  Selectivity

Gating of Voltage-Gated Cation-Permeant Channels is Caused by
Movement of S4 a-Helices in Response to a Change in V_m

P-Loops Form the Selectivity Filter of
Voltage-Gated Cation-Permeant Channels

Voltage-Gated Ion Channel
Gene Superfamilies

Voltage-Gated Cl^- Channels Differ in Sequence and Structure from Cation-Permeant Channels

Voltage-Gated  Cl^- Channels are Dimers