2001B05 Describe the structure and function of voltage-gated ion channels.

Key features

·   Often many subunits

·   Ion channel: selective for ion or charge

·   Activation and inactivation gates

·   Voltage sensor

Example

·   Voltage-dependent Na⁺ channel (VDNaC)

Background

·   The lipid bilayer is impermeable to ions

·   Ions can only travel through channels

·   Direct of passage determined by electrochemical gradient

·   Gradient established by active transport e.g. Na⁺K⁺ATPase

How it works

·   Rapid cycling through states (resting -> activated -> inactivated)

·   Triggered by changes in local potential difference

Purpose

·   Allows rapid and co-ordinated propagation of signals

·   Important in excitable tissues

Role in action potentials

·   Nerve: (Na⁺, K⁺ channels)

·   Myocardial ventricular muscle (Na⁺, Ca²⁺, K⁺ channels)

·   AV node (pacemaker potential) (I_f, Ca²⁺, K⁺ channels)

Causes of dysfunction

·   Local anaesthetics: inhibit VDNaC in peripheral nerves

·   Tetrodotoxin: inhibits VDNaC in peripheral nerves

·   Eaton-Lambert syndrome: inhibit pre-synaptic VDCC (Ca²⁺)

State

Membrane potential

Activation gate

Inactivation gate

Resting

-90mV

Closed

Closed

Activated

-70 to +30mV

Open

Open

Inactivated

+30 to -70mV

Open

Closed