Difference between revisions of "Ligand-gated ion channel"

Latest revision as of 21:12, 21 September 2010

Ligand-gated ion channels (LGICs) are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger (i.e., a ligand),^[1] such as a neurotransmitter.^[2]

The binding site of endogenous ligands on LGICs protein complexes are normally located on a different portion of the protein (an allosteric binding site) compared to where the ion conduction pore is located. The direct link between ligand binding and opening or closing of the ion channel, which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of metabotropic receptors, which use second messengers. LGICs are also different from voltage-gated ion channels (which open and close depending on membrane potential), and stretch-activated ion channels (which open and close depending on mechanical deformation of the cell membrane).^[2][3]

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.

Structure

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.^[4]

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 allowed 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

Many important ion channels are ligand-gated, and they show a significant degree of homology at the genetic level. LGICs are classified into three superfamilies:

Cys-loop receptors

The cys-loop receptors contain a characteristic loop formed by a disulfide bond between two cysteine residues and are subdivided into the type of ion that the corresponding channel conducts (anionic or cationic) and further into families defined by the endogenous ligand. They are usually pentameric.

Vertebrate Anionic Cys-loop Receptors

Vertebrate Cationic Cys-loop Receptors

Ionotropic glutamate receptors

The glutamate receptors bind the neurotransmitter glutamate. They form tetramers.

ATP-gated channels

ATP-gated channels open in response to binding the nucleotide ATP. They form trimers.

Clinical relevance

Ligand-gated ion channels are likely to be the major site at which anaesthetic agents and ethanol have their effects, although unequivocal evidence of this is yet to be established.^[7][8] In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.^[9]

See also

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References

External links

• Ligand-Gated Ion Channel database at European Bioinformatics Institute. Verified availability April 11, 2007.
• "Revised Recommendations for Nomenclature of Ligand-Gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

fa:کانال یونی دریچه-لیگاندی fr:Récepteur ionotrope it:Recettore ionotropico ko:리간드 개폐 통로 nl:Ionotrope receptor

1. ↑ ligand-gated channel at Dorland's Medical Dictionary
2. ↑ ^{2.0 2.1} Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates. pp. 156–7. ISBN 978-0-87893-697-7. CS1 maint: Multiple names: authors list (link)
3. ↑ 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. 
4. ↑ 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. 
5. ↑ ^{5.0 5.1 5.2 5.3} Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
6. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
7. ↑ 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. PMC 2854026 Freely accessible. PMID 10487207. 
8. ↑ Dilger JP (2002). "The effects of general anaesthetics on ligand-gated ion channels". Br J Anaesth. 89 (1): 41–51. doi:10.1093/bja/aef161. PMID 12173240. 
9. ↑ Harris RA, Mihic SJ, Dildy-Mayfield JE, Machu TK (1995). "Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition" (abstract). FASEB J. 9 (14): 1454–62. PMID 7589987. CS1 maint: Multiple names: authors list (link)