[[Image:LGIC.png|thumb|400px|Ligand-gated ion channel]]
[[Image:LGIC.png|thumb|400px|Ligand-gated ion channel]]
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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 channel]]sor [[stretch-activatedionchannel]]s.
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'''Ligand-gated ion channels''' ('''LGICs'''), also referred to as '''ionotropic receptors''' or '''channel-linked receptors''', are a group of [[transmembrane]][[ion channel]]s that are opened or closed in response to the binding of a chemical messenger (i.e., a [[ligand (biochemistry)|ligand]]),<ref>{{DorlandsDict|two/000019817|ligand-gated channel}}</ref>such as a [[neurotransmitter]].<ref name="Purves" >{{cite book | author = Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-SamuelLaMantia,James O. McNamara, and Leonard E. White | title = Neuroscience. 4th ed. | publisher = Sinauer Associates | pages = 156–7 | year = 2008 | isbn = 978-0-87893-697-7}}</ref>
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The [[ion channel]] isregulatedby a [[neurotransmitter]] [[ligand]] and is usuallyveryselectivetoone or moreionslike[[sodium|Na<sup>+</sup>]], [[potassium|K<sup>+</sup>]], [[calcium|Ca<sup>2+</sup>]], or [[chloride|Cl<sup>-</sup>]]. Suchreceptorslocatedat [[synapse]]s convertthechemicalsignalof [[presynaptic]]allyreleasedneurotransmitterdirectly and veryquicklyintoa [[postsynaptic]] electricalsignal.
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The binding site of [[Endogeny#Biology|endogenous]] ligandsonLGICs protein complexes are normally located on a different portion of the protein (an [[allosteric regulation|allosteric]] binding site) compared to where the ion conduction pore is located.Thedirectlinkbetween ligand binding and opening or closingoftheion channel, which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of [[metabotropic receptor]]s, which use [[Second messenger system|second messenger]]s. Ligand-gatedionchannelsare also different from [[voltage-gated ion channel]]s (whichopenandclosedepending on [[membrane potential]]),and[[stretch-activatedion channel]]s (which open and closedependingonmechanical deformation of the [[cell membrane]]).<refname="Purves"/><ref name="pmid15157178">{{cite journal | author = Connolly CN, Wafford KA | title = The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function | journal = Biochem. Soc. Trans. | volume = 32 | issue = Pt3 | pages = 529–34 | year = 2004 | pmid = 15157178 | doi = 10.1042/BST0320529 }}</ref>
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Thisis in contrast to the more slowly signaling [[metabotropic receptor]]s which are not themselves ion channels but rather may be linked to them through complex [[intracellular]] [[second messenger]] cascades (e.g. [[G protein-coupled receptor]]s). Many LGICs are additionally modulated by [[allosteric]] [[ligand]]s, by [[channel blockers]], [[ion]]s, or the [[membrane potential]].
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==Regulation==
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The prototypic ligand-gated ion channel is the [[nicotinic acetylcholine receptor]].Itconsistsof a pentamer of protein subunits, with two binding sites for [[acetylcholine]], which, when bound, alter the receptor's configuration and causeaninternalpore to open.Thispore,permeable to Na<sup>+</sup>, allows Na<sup>+</sup> ions to flow down their [[electrochemical gradient]] into the cell. With a sufficient number of channels opening at once, theintracellular Na<sup>+</sup> concentrationrisestothepointat which the positivechargewithin the [[cell (biology)|cell]] isenoughtodepolarizethe[[cellmembrane|membrane]],and an [[action potential]] isinitiated.
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The [[ion channel]] isregulatedby a [[Ligand (biochemistry)|ligand]] and isusuallyveryselective to oneormoreionslike[[sodium|Na<sup>+</sup>]], [[potassium|K<sup>+</sup>]], [[calcium|Ca<sup>2+</sup>]], or[[chloride|Cl<sup>-</sup>]].Suchreceptorslocatedat[[synapse]]sconvert the chemicalsignalof [[presynaptic]]allyreleasedneurotransmitterdirectlyandveryquicklyintoa [[postsynaptic]] electricalsignal.
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The''Ligand-gated ion channels'' are classifiedintofoursuperfamilies:the''Cys''-loop receptors, the [[glutamatereceptor]]s, theTRP (transient receptor potential) channels and the [[Adenosinetriphosphate|ATP]]-gated channels.
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ManyLGICs are additionallymodulatedby[[allosteric]][[Ligand(biochemistry)|ligands]], by [[channelblockers]], [[ion]]s,or the [[membranepotential]].
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Many important ion channels are ligand-gated, including [[GABA receptor|GABA]], [[NMDA receptor|NMDA]], [[acetylcholine receptor|acetylcholine]], [[glycine receptor]]s, and the 5-HT<sub>3</sub> [[serotonin]] receptor, and they show a great degree of homology at the genetic level.
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==Structure==
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Each subunit of the [[pentamer|pentameric]] channels consist of the extracellular ligand-binding domain and a transmembrane domain. Each transmembrane domain in the pentamer includes four [[transmembrane helix]]es.<ref name="pmid15023997">{{cite journal | author = Cascio M | title = Structure and function of the glycine receptor and related nicotinicoid receptors | journal = J. Biol. Chem. | volume = 279 | issue = 19 | pages = 19383–6 | year = 2004 | pmid = 15023997 | doi = 10.1074/jbc.R300035200 }}</ref>
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''Ligand-gatedionchannels''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.
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==Example:nicotinicacetylcholinereceptor==
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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 allows Na<sup>+</sup> ions to flow down their [[electrochemical gradient]] into the cell. With a sufficient number of channels opening at once, the intracellular Na<sup>+</sup> concentration rises to the point at which the positive charge within the [[cell (biology)|cell]] is enough to depolarize the [[cell membrane|membrane]], and an [[action potential]] is initiated.
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== Also Known As: ==
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== Classification ==
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ChemicallyGatedIonChannels.
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Manyimportantionchannels are ligand-gated, and they show a significant degree of [[Homology_(biology)|homology]] at the genetic level. LGICs are classified into three superfamilies:
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=== Cys-loop receptors ===
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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.
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'''Anionic'''
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{| class="wikitable"
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|-
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! Type
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! Class
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! IUPHAR-recommended <br> protein name <ref name="IUPHAR">{{cite journal |author= Collingridge GL, Olsen RW, Peters J, Spedding M|title=A nomenclature for ligand-gated ion channels.|journal= Neuropharmacology |volume= Epub ahead of print |issue= |pages= |year= 2008 |pmid= 18655795 | doi = 10.1016/j.neuropharm.2008.06.063}}</ref>
''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.<ref name="pmid10487207">{{cite journal | author = Krasowski MD, Harrison NL | title = General anaesthetic actions on ligand-gated ion channels | journal = Cell. Mol. Life Sci. | volume = 55 | issue = 10 | pages = 1278–303 | year = 1999 | pmid = 10487207 | doi = 10.1007/s000180050371 }}</ref><ref name="pmid12173240">{{cite journal | author = Dilger JP | title = The effects of general anaesthetics on ligand-gated ion channels | journal = Br J Anaesth | volume = 89 | issue = 1 | pages = 41–51 | year = 2002 | pmid = 12173240 | doi = 10.1093/bja/aef161 }}</ref> In particular, the [[GABA]] and [[NMDA]] receptors are affected by [[anaesthetic]] agents at concentrations similar to those used in clinical anaesthesia.<ref name="pmid7589987">{{cite journal | author = Harris RA, Mihic SJ, Dildy-Mayfield JE, Machu TK | title = Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition | journal = FASEB J. | volume = 9 | issue = 14 | pages = 1454–62 | year = 1995 | pmid = 7589987 | doi = | issn = | url = http://www.fasebj.org/cgi/content/abstract/9/14/1454 | format = abstract }}</ref>
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== See also ==
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{{multicol}}
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*[[Chronotropic]]
*[[Receptor (biochemistry)]]
*[[Receptor (biochemistry)]]
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*[[NMDA receptor]]
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*[[AMPA receptor]]
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*[[Kainate receptor]]
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*[[Nicotinic acetylcholine receptor]]
*[[Glycine receptor]]
*[[Glycine receptor]]
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*[[GABA receptor|GABA<sub>A</sub> receptor]]
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{{multicol-break}}
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*[[5-HT3receptor|5-HT<sub>3</sub> receptor]]
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*[[P2XReceptor]]
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*[[P2XReceptors]]
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*[[Sodiumion channel]]
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*[[Metabotropic receptor]]
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{{multicol-end}}
== References ==
== References ==
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*''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''
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{{Reflist|2}}
== External links ==
== External links ==
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* [http://www.ebi.ac.uk/compneur-srv/LGICdb/LGICdb.php Ligand-Gated Ion Channeldatabase].VerifiedavailabilityJuly11,2005.
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*{{cite web | url = http://www.iuphar-db.org/LGICNomenclature.jsp | title = Revised Recommendations for Nomenclature of Ligand-Gated Ion Channels|accessdate=|author= | authorlink = | coauthors = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}
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* [http://www.ebi.ac.uk/compneur-srv/LGICdb/LGICdb.php Ligand-Gated Ion Channel database] at [[European Bioinformatics Institute]]. Verified availability April 11, 2007.
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==Further reading==
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*{{cite journal | author=Collingridge GL, Olsen RW, Peters J, Spedding M |title=A nomenclature for ligand-gated ion channels |journal=Neuropharmacology |volume= Epub ahead of print|issue= |pages= |year= 2008 |pmid= 18655795| doi:10.1016/j.neuropharm.2008.06.063}}
Ligand-gated ion channels (LGICs), also referred to as ionotropic receptors or channel-linked receptors, are a group of transmembraneion 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. Ligand-gated ion channels 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]
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.[4]
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 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.
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:
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.
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]
↑ 2.02.1Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed., 156–7, Sinauer Associates.
↑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.
↑Cascio M (2004). Structure and function of the glycine receptor and related nicotinicoid receptors. J. Biol. Chem.279 (19): 19383–6.
↑ 5.05.15.25.3Collingridge GL, Olsen RW, Peters J, Spedding M (2008). A nomenclature for ligand-gated ion channels.. NeuropharmacologyEpub ahead of print.
↑A</sub>">Olsen RW, Sieghart W (2008). International Union of Pharmacology. LXX. Subtypes of γ-aminobutyric acidA receptors: classification on the basis of subunit composition, pharmacology, and function. Update.. Pharmacol. Rev.60: 243-60.
↑Krasowski MD, Harrison NL (1999). General anaesthetic actions on ligand-gated ion channels. Cell. Mol. Life Sci.55 (10): 1278–303.
↑Dilger JP (2002). The effects of general anaesthetics on ligand-gated ion channels. Br J Anaesth89 (1): 41–51.
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