The Ligand-gated ion channels, also referred to as 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 metabotropic receptors which signal slowly 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. When these two binding sites are bound to acetylcholine, the receptor's configuration changes and an internal pore opens to allow influx of Na+ ions into the cell. With a sufficient number of channels opening at once, the intracellular Na+ concentration rises to the point where the cell membrane depolarises 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 and glycine receptors, and they show a great degree of homology at the genetic level.
Ligand-gated ion channels are likely to be the major site that anaesthetic agents mediate 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.
References
- The Cys-loop superfamily of ligand-gated ion channels - the impact of receptor structure on function (1984) Connolly, C. N. & Wafford, K. A., in Biochemical Society Transactions (2004) Vol. 32
See also