Ligand-gated ion channel



The Ligand-gated ion channels, also referred to as LGICs, or ionotropic receptors, are a group of intrinsic transmembrane ion channels that are opened in response to binding of a chemical messenger, as opposed to voltage-gated ion channels or stretch-activated ion channels.

The ion channel is regulated by a neurotransmitter ligand and is usually very selective to one or more ions like Na+, K+, Ca2+, or Cl-. Such receptors located at synapses convert the chemical signal of presynaptically released neurotransmitter directly and very quickly into a postsynaptic electrical signal.

This is in contrast to the more slowly signaling metabotropic receptors which are not themselves ion channels but rather may be linked to them through complex intracellular second messenger cascades (e.g. G protein-coupled receptors). Many LGICs are additionally modulated by allosteric ligands, by channel blockers, ions, or the membrane potential.

The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor. It consists of a pentamer of protein subunits, with two binding sites for acetylcholine, which, when bound, alter the receptor's configuration and cause an internal pore to open. This pore, permeable to Na+, allows Na+ ions to flow down their electrochemical gradient into the cell. With a sufficient number of channels opening at once, the intracellular Na+ concentration rises to the point at which the positive charge within the cell is enough to depolarize the membrane, and an action potential is initiated.

The Ligand-gated ion channels are classified into four superfamilies: the Cys-loop receptors, the glutamate receptors, the TRP (transient receptor potential) channels and the ATP-gated channels.

Many important ion channels are ligand-gated, including GABA, NMDA, acetylcholine, glycine receptors, and the 5-HT3 serotonin receptor, and they show a great degree of homology at the genetic level.

Ligand-gated ion channels are likely to be the major site at which anaesthetic agents have their effects, although unequivocal evidence of this is yet to be established. In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.

Also Known As:
Chemically Gated Ion Channels.