Ion channels

Abstract

Ion channels are protein-lined pores that span membranes and allow ions to move in the direction favoured by the cell's electrical and chemical gradients. Although ion channels are diverse, most share two key functional features. First, most ion channels exhibit ion selectivity (i.e. only conduct a limited range of ions and distinguish between ionic species on the basis of charge and size). Second, the opening or closing (or gating) of most ion channels is tightly controlled. A variety of gating mechanisms are known but the two most important are voltage-gating and ligand-gating. At voltage-gated channels, opening or closing is controlled by changes in the cell's membrane potential. For most channels in this category, opening becomes more likely as the membrane becomes more depolarized. Voltage-gated channels are usually subdivided on the basis of ion selectivity, into sodium channels, potassium channels and calcium channels. The mechanism of several important drug classes centres around this type of channel: local anaesthetics and class 1 antiarrhythmic drugs act by blocking sodium channels, while calcium antagonists (e.g. verapamil) block voltage-gated calcium channels. By contrast, ligand-gated channels are opened when an extracellular neurotransmitter molecule binds to the channel. This type of channel is usually classified according to its neurotransmitter ligand and ligand-gated channels activated by acetylcholine, serotonin (5-HT), glycine, glutamate and g-aminobutyric acid have been described. Ligand-gated channels also include important drug targets. Many neuromuscular blocking agents and a variety of anxiolytic and hypnotic drugs act at this type of channel.