Ligand-gated ion channel
1351369
224552882
2008-07-09T11:15:27Z
Boghog2
2428506
simplification
[[Image:LGIC.png|thumb|300px|Ligand-gated ion channel]]
{{Pfam_box
| Symbol = Neur_chan_memb
| Name = Neurotransmitter-gated ion-channel transmembrane region
| image =2bg9 opm.gif
| width = 300px
| caption =
| Pfam= PF02932
| InterPro= IPR006029
| SMART=
| PROSITE= PDOC00209
| SCOP = 1cek
| TCDB = 1.A.9
| OPM family= 14
| OPM protein= 2bg9
| PDB=
{{PDB3|1oed}}E:242-483 {{PDB3|2bg9}}E:242-389 {{PDB3|1dxz}}A:260-291
{{PDB3|3mra}} :301-325 {{PDB3|1a11}} :276-298 {{PDB3|1cek}}A:276-298
{{PDB3|1eq8}}E:276-298 {{PDB3|1mot}}A:277-304 {{PDB3|1vry}}A:281-337
}}
{{Pfam_box
| Symbol = Neur_chan_LBD
| Name = Neurotransmitter-gated ion-channel ligand binding domain
| image =
| width =
| caption =
| Pfam= PF02931
| InterPro= IPR006202
| SMART=
| Prosite = PDOC00209
| SCOP = 1lxg
| TCDB =
| OPM family=
| OPM protein=
| PDB=
{{PDB3|1ux2}}F:34-142 {{PDB3|1uw6}}D:34-142 {{PDB3|1i9b}}E:34-142
{{PDB3|1uv6}}J:34-142 {{PDB3|1yi5}}A:34-142 {{PDB3|2bys}}D:23-226
{{PDB3|2byr}}I:23-226 {{PDB3|2byq}}A:23-226 {{PDB3|2br7}}D:23-226
{{PDB3|2byp}}C:23-225 {{PDB3|2byn}}A:23-226 {{PDB3|2bg9}}B:28-241
{{PDB3|1lk1}}G:28-241 {{PDB3|1olk}}E:28-241 {{PDB3|1ol8}}B:26-230
{{PDB3|1ol3}}A:26-230 {{PDB3|1ol4}}B:26-230 {{PDB3|1kl8}}B:201-219
{{PDB3|1kc4}}B:201-219 {{PDB3|1ol9}}A:26-230 {{PDB3|1y5t}}B:230-235
{{PDB3|1l4w}}B:206-226 {{PDB3|1ljz}}B:206-226 {{PDB3|1idg}}B:205-222
{{PDB3|1tos}} :91-99 {{PDB3|1lxg}}B:205-222 {{PDB3|1lxh}}B:205-222
{{PDB3|1idh}}B:205-222 {{PDB3|1tor}} :91-100 {{PDB3|1ole}}A:39-245
{{PDB3|1olf}}A:29-235 {{PDB3|1olj}}C:29-235
}}
{{portalpar|Neuroscience|Neuro logo.png}}
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 channel]]s or [[stretch-activated ion channel]]s.<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>
==Regulation==
The [[ion channel]] is regulated by a [[Ligand (biochemistry)|ligand]] and is usually very selective to one or more ions like [[sodium|Na<sup>+</sup>]], [[potassium|K<sup>+</sup>]], [[calcium|Ca<sup>2+</sup>]], or [[chloride|Cl<sup>-</sup>]]. Such receptors located at [[synapse]]s convert the chemical signal of [[presynaptic]]ally released neurotransmitter directly and very quickly into a [[postsynaptic]] electrical signal.
Many LGICs are additionally modulated by [[allosteric]] [[Ligand (biochemistry)|ligands]], by [[channel blockers]], [[ion]]s, 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 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>
==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<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, 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.
==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
** [[GABAA receptor|GABA]]<sub>A</sub>
*** [[GABRA1|α<sub>1</sub>]] ({{Gene|GABRA1}}), [[GABRA2|α<sub>2</sub>]] ({{Gene|GABRA2}}), [[GABRA3|α<sub>3</sub>]] ({{Gene|GABRA3}}), [[GABRA4|α<sub>4</sub>]] ({{Gene|GABRA4}}), [[GABRA5|α<sub>5</sub>]] ({{Gene|GABRA5}}), [[GABRA6|α<sub>6</sub>]] ({{Gene|GABRA6}})
*** [[GABRB1|β<sub>1</sub>]] ({{Gene|GABRB1}}), [[GABRB2|β<sub>2</sub>]] ({{Gene|GABRB2}}), [[GABRB3|β<sub>3</sub>]] ({{Gene|GABRB3}})
*** [[GABRG1|γ<sub>1</sub>]] ({{Gene|GABRG1}}), [[GABRG2|γ<sub>2</sub>]] ({{Gene|GABRG2}}), [[GABRG3|γ<sub>3</sub>]] ({{Gene|GABRG3}})
*** [[GABRD|δ]] ({{Gene|GABRD}}), [[GABRE|ε]] ({{Gene|GABRE}}), [[GABRP|π]] ({{Gene|GABRP}}), [[GABRQ|θ]] ({{Gene|GABRQ}})
** [[GABAC receptor|GABA]]<sub>C</sub>
*** [[GABRR1|ρ<sub>1</sub>]] ({{Gene|GABRR1}}), [[GABRR2|ρ<sub>2</sub>]] ({{Gene|GABRR2}}), [[GABRR3|ρ<sub>3</sub>]] ({{Gene|GABRR3}})
** [[glycine receptor|Glycine]] (GlyR)
*** [[GLRA1|α<sub>1</sub>]] ({{Gene|GLRA1}}), [[GLRA2|α<sub>2</sub>]] ({{Gene|GLRA2}}), [[GLRA3|α<sub>3</sub>]] ({{Gene|GLRA3}}), [[GLRA4|α<sub>4</sub>]] ({{Gene|GLRA4}})
*** [[GLRB|β]] ({{Gene|GLRB}})
* cationic
** 5-HT<sub>3</sub> [[5-HT3 receptor|serotonin receptor]]
*** [[HTR3A|5-HT<sub>3A</sub>]] ({{Gene|HTR3A}}), [[HTR3B|5-HT<sub>3B</sub>]] ({{Gene|HTR3B}}), [[HTR3C|5-HT<sub>3C</sub>]] ({{Gene|HTR3C}}), [[HTR3D|5-HT<sub>3D</sub>]] ({{Gene|HTR3D}}), [[HTR3E|5-HT<sub>3E</sub>]] ({{Gene|HTR3E}})
** [[nicotinic acetylcholine receptor]] (nAChR)
*** [[CHRNA1|α<sub>1</sub>]] ({{Gene|CHRNA1}}), [[CHRNA2|α<sub>2</sub>]] ({{Gene|CHRNA2}}), [[CHRNA3|α<sub>3</sub>]] ({{Gene|CHRNA3}}), [[CHRNA4|α<sub>4</sub>]] ({{Gene|CHRNA4}}), [[CHRNA5|α<sub>5</sub>]] ({{Gene|CHRNA5}}), [[CHRNA6|α<sub>6</sub>]] ({{Gene|CHRNA6}}), [[CHRNA7|α<sub>7</sub>]] ({{Gene|CHRNA7}}), [[CHRNA9|α<sub>9</sub>]] ({{Gene|CHRNA9}}), [[CHRNA10|α<sub>10</sub>]] ({{Gene|CHRNA10}})
*** [[CHRNB1|β<sub>1</sub>]] ({{Gene|CHRNB1}}), [[CHRNB2|β<sub>2</sub>]] ({{Gene|CHRNB2}}), [[CHRNB3|β<sub>3</sub>]] ({{Gene|CHRNB3}}), [[CHRNB4|β<sub>4</sub>]] ({{Gene|CHRNB4}})
*** [[CHRND|δ]] ({{Gene|CHRND}}), [[CHRNE|ε]] ({{Gene|CHRNE}}), [[CHRNG|γ]] ({{Gene|CHRNG}})
===The ionotropic [[glutamate receptor]]s===
*[[AMPA receptor|AMPA]]
** [[GRIA1|GluR<sub>1</sub>]] ({{Gene|GRIA1}}), [[GRIA2|GluR<sub>2</sub>]] ({{Gene|GRIA2}}), [[GRIA3|GluR<sub>3</sub>]] ({{Gene|GRIA3}}), [[GRIA4|GluR<sub>4</sub>]], alternatively called GluRA-D ({{Gene|GRIA4}})
*[[Kainate receptor|Kainate]]
** [[GRIK1|GluR<sub>5]]</sub> ({{Gene|GRIK1}}), [[GRIK2|GluR<sub>6</sub>]] ({{Gene|GRIK2}}), [[GRIK3|GluR<sub>7</sub>]] ({{Gene|GRIK3}})
** [[GRIK4|KA<sub>1</sub>]] ({{Gene|GRIK4}}), [[GRIK5|KA<sub>2</sub>]] ({{Gene|GRIK5}})
*[[NMDA receptor|NMDA]]
** [[GRIN1|NR1]] ({{Gene|GRIN1}})
** [[GRIN2A|NR2A]] ({{Gene|GRIN2A}}), [[GRIN2B|NR2B]] ({{Gene|GRIN2B}}), [[GRIN2C|NR2C]] ({{Gene|GRIN2C}}), [[GRIN2D|NR2D]] ({{Gene|GRIN2D}}), [[GRIN3A|NR3A]] ({{Gene|GRIN3A}}), [[GRIN3B|NR3B]] ({{Gene|GRIN3B}}), [[GRINL1A|NRL1A]] ({{Gene|GRINL1A}}), [[GRINL1B|NRL1B]] ({{Gene|GRINL1B}})
===The [[Adenosine triphosphate|ATP]]-gated channels===
*[[P2X Receptor|P2X]]
** [[P2RX1|P2X<sub>1</sub>]] ({{gene|P2RX1}}), [[P2RX2|P2X<sub>2</sub>]] ({{gene|P2RX2}}), [[P2RX3|P2X<sub>3</sub>]] ({{gene|P2RX3}}), [[P2RX1|P2X<sub>4</sub>]] ({{gene|P2RX4}}), [[P2RX1|P2X<sub>5</sub>]] ({{gene|P2RX5}}), [[P2RX1|P2X<sub>6</sub>]] ({{gene|P2RX6}}), [[P2RX7|P2X<sub>7</sub>]] ({{gene|P2RX7}})
==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.<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>
== See also ==
*[[Chronotropic]]
*[[Receptor (biochemistry)]]
*[[Glycine receptor]]
*[[P2X Receptor]]
*[[Sodium ion channel]]
== References ==
{{Reflist|2}}
== External links ==
* [http://www.ebi.ac.uk/compneur-srv/LGICdb/LGICdb.php Ligand-Gated Ion Channel database] at [[European Bioinformatics Institute]]. Verified availability April 11, 2007.
{{Ion channels}}
{{Ligand-gated ion channels}}
[[Category:Membrane biology]]
[[Category:Ion channels]]
[[Category:Electrophysiology]]
[[Category:Ionotropic receptors]]
[[Category:Neurochemistry]]
[[Category:Molecular neuroscience]]
[[de:Ionotroper Rezeptor]]
[[fr:Récepteur ionotropique]]
[[it:Recettore ionotropico]]
[[pl:Receptor jonotropowy]]