Ligand-gated ion channel

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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 or closed in response to binding of a chemical messenger, as opposed to voltage-gated ion channels or stretch-activated ion channels.

Regulation

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.

Many LGICs are additionally modulated by allosteric ligands, by channel blockers, ions, or the membrane potential.

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:

The Cys-loop receptors

• anionic
  • GABA_A
  • GABA_C
  • Glycine
• cationic
  • 5-HT₃ serotonin receptor
  • nicotinic acetylcholine receptor

The ionotropic glutamate receptors

• NMDA
• Kainate
• AMPA

The ATP-gated channels

• P2X

Clinical relevance

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.

See also

• Chronotropic
• Receptor (biochemistry)
• Glycine receptor
• P2X Receptor
• Sodium ion channel

References

• Connolly, CN (2004). "The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function". Biochem. Soc. Trans. 32 (3): 529–534. ISSN 0300-5127. PMID 15157178. Retrieved 2007-06-08.

External links

• Ligand-Gated Ion Channel database at European Bioinformatics Institute. Verified availability April 11, 2007.