Voltage-gated ion channels have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change.

[1] The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.

The functionality of voltage-gated ion channels is attributed to its three main discrete units: the voltage sensor, the pore or conducting pathway, and the gate.

This movement of ions down their concentration gradients subsequently generates an electric current sufficient to depolarize the cell membrane.

It is thought that the first 4 arginines account for the gating current, moving toward the extracellular solvent upon channel activation in response to membrane depolarization.

[7] Movement of the voltage-sensor triggers a conformational change of the gate of the conducting pathway, controlling the flow of ions through the channel.

[3] The main functional part of the voltage-sensitive protein domain of these channels generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence, interchangeable across a wide variety of cells and species.

The gate is thought to be coupled to the voltage sensing regions of the channels and appears to contain a mechanical obstruction to ion flow.

While ten human genes encoding for sodium channels have been identified, their function is typically conserved between species and different cell types.

In most cells, Ca2+ channels regulate a wide variety of biochemical processes due to their role in controlling intracellular Ca2+ concentrations.

This difference in activation time influences the duration and rate of action potential firing, which has a significant effect on electrical conduction along an axon as well as synaptic transmission.

[1] Voltage-gated proton channels carry currents mediated by hydrogen ions in the form of hydronium, and are activated by depolarization in a pH-dependent manner.