Voltage-gated ion channels

Ion channels

Membrane proteins that allow ions to cross the lipid bilayer and are essential for generating action potentials.

Voltage-gated ion channels (VGICs)

Channels that open or close in response to changes in membrane potential, enabling rapid electrical signalling.

VGNaC / NaV channel

A voltage-gated Na⁺ channel selective for Na⁺ and responsible for the rapid upstroke of the action potential.

VGKC / KV channel

A voltage-gated K⁺ channel responsible for repolarisation and the relative refractory period.

Importance of ion channels

They underpin neuronal and muscle excitability; defects cause neurological and muscular diseases in humans and animals.

Local anaesthetics

Drugs that enter NaV channels from inside the axon and block them, preventing action potential generation in pain fibres.

C-fibre nociceptors

Small unmyelinated sensory fibres detecting noxious stimuli; especially important in veterinary pain management.

Voltage clamp

A technique that holds membrane voltage constant to measure ionic currents underlying action potentials.

Hodgkin & Huxley voltage-clamp discovery

Revealed fast inward Na⁺ current and delayed outward K⁺ current during depolarisation.

Fast inward current

Rapid Na⁺ influx through VGNaCs when the membrane is depolarised.

Delayed outward current

Slower K⁺ efflux through VGKCs contributing to repolarisation.

Voltage-dependent gating

The mechanism where changes in membrane potential alter the conformation of VGICs to open or close.

S4 voltage sensor

A positively charged helical segment in each channel domain that moves in response to voltage, triggering channel opening.

Pore loop (S5-S6)

Region of the channel responsible for ion selectivity and forming the ion conduction pathway.

NaV channel structure

One α-subunit containing 4 domains with 6 transmembrane segments each, arranged around a central pore.

NaV inactivation gate

A segment that rapidly blocks the pore ~1 ms after opening, producing the absolute refractory period.

Orthodromic conduction

One-way propagation of action potentials ensured by NaV channel inactivation.

Local anaesthetic binding site

Region near the S6 helix of domain IV in NaV channels where local anaesthetics bind.

Voltage-dependent block

Local anaesthetics bind only when the NaV channel is open, meaning active fibres are blocked first.

KV channel structure

Four separate α-subunits assemble to form one functional channel, each with 6 transmembrane regions.

KV delayed activation

K⁺ channels open more slowly than Na⁺ channels, explaining action potential repolarisation timing.

Ball-and-chain inactivation

A mechanism present in some KV channels where an inactivation particle rapidly blocks the pore.

Squid giant axon example

A classic neurophysiology model with very large axons used to study VGICs; foundational for action potential research.

Electric eel VGNaC source

Provided abundant NaV protein, enabling sequencing and structural studies of the channel.

Xenopus oocyte expression

Frog oocytes used experimentally to express mutated or isolated ion channels to study their function.

Patch clamp technique

Allows recording of currents from a single ion channel by forming a high-resistance seal with a pipette.

Single-channel behaviour

Channels flicker rapidly between open/closed states in a probabilistic (stochastic) manner.

Popen (open probability)

The proportion of time an ion channel is open at a given voltage, affected by gating and prior state.

Single-channel conductance

The current carried by an individual channel, following Ohm’s law and depending on ion concentration.

Channelopathies

Diseases caused by mutated ion channels; occur in both humans and domestic animals.

Congenital myotonia in dogs

A veterinary channelopathy caused by mutated Cl⁻ or Na⁺ channels, producing delayed muscle relaxation.

Congenital insensitivity to pain

Caused by NaV channel mutations; rare but important for understanding sensory dysfunction.

Role of VGNaCs in AP threshold

Opening of NaV channels produces inward Na⁺ current that drives the membrane to threshold.

Role of VGKCs in refractory period

K⁺ efflux hyperpolarises the membrane, requiring stronger stimuli for another action potential.

VGICs in sensory afferents

Underlie the rapid signalling from muscle spindles and nociceptors essential in veterinary neurological exams.