The Ligand-gated ion channels, also referred to as LGICs, or ionotropic receptors, are a group of intrinsic transmembrane ion channels that are opened or closed in response to binding of a chemical messenger, as opposed to voltage-gated ion channels or stretch-activated ion channels.[1]
The ion channel is regulated by a 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.
Each subunit of the pentameric channels consist of the extracellular ligand-binding domain and a transmembrane domain. Each transmembrane domain in the pentamer includes four transmembrane helixes.[2]
Example: nicotinic acetylcholine receptor
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.
Classification and examples
Many important ion channels are ligand-gated, and they show a great degree of homology at the genetic level. The Ligand-gated ion channels are classified into three superfamilies:
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.[3][4] In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.[5]
^ Connolly CN, Wafford KA (2004). "The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function". Biochem. Soc. Trans.32 (Pt3): 529–34. doi:10.1042/BST0320529. PMID 15157178.
^ Cascio M (2004). "Structure and function of the glycine receptor and related nicotinicoid receptors". J. Biol. Chem.279 (19): 19383–6. doi:10.1074/jbc.R300035200. PMID 15023997.
^ Krasowski MD, Harrison NL (1999). "General anaesthetic actions on ligand-gated ion channels". Cell. Mol. Life Sci.55 (10): 1278–303. doi:10.1007/s000180050371. PMID 10487207.
^ Dilger JP (2002). "The effects of general anaesthetics on ligand-gated ion channels". Br J Anaesth89 (1): 41–51. doi:10.1093/bja/aef161. PMID 12173240.
^ Harris RA, Mihic SJ, Dildy-Mayfield JE, Machu TK (1995). "Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition". FASEB J.9 (14): 1454–62. PMID 7589987.