Editing Ion channel (section)

==== Lipid-gated ====
{{Main|Lipid-gated ion channels}}

This group of channels opens in response to specific [[lipid]] molecules binding to the channel's transmembrane domain typically near the inner leaflet of the plasma membrane.<ref>{{cite journal | vauthors = Hansen SB | title = Lipid agonism: The PIP2 paradigm of ligand-gated ion channels | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1851 | issue = 5 | pages = 620–8 | date = May 2015 | pmid = 25633344 | pmc = 4540326 | doi = 10.1016/j.bbalip.2015.01.011 }}</ref> Phosphatidylinositol 4,5-bisphosphate ([[Phosphatidylinositol 4,5-bisphosphate|PIP<sub>2</sub>]]) and phosphatidic acid ([[Phosphatidic acid|PA]]) are the best-characterized lipids to gate these channels.<ref>{{cite journal | vauthors = Hansen SB, Tao X, MacKinnon R | title = Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2 | journal = Nature | volume = 477 | issue = 7365 | pages = 495–8 | date = August 2011 | pmid = 21874019 | pmc = 3324908 | doi = 10.1038/nature10370 | bibcode = 2011Natur.477..495H }}</ref><ref>{{cite journal | vauthors = Gao Y, Cao E, Julius D, Cheng Y | title = TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action | journal = Nature | volume = 534 | issue = 7607 | pages = 347–51 | date = June 2016 | pmid = 27281200 | pmc = 4911334 | doi = 10.1038/nature17964 | bibcode = 2016Natur.534..347G }}</ref><ref>{{cite journal | vauthors = Cabanos C, Wang M, Han X, Hansen SB | title = 2 Antagonism of TREK-1 Channels | journal = Cell Reports | volume = 20 | issue = 6 | pages = 1287–1294 | date = August 2017 | pmid = 28793254 | pmc = 5586213 | doi = 10.1016/j.celrep.2017.07.034 }}</ref> Many of the leak potassium channels are gated by lipids including the [[Inward-rectifier potassium ion channel|inward-rectifier potassium channels]] and two pore domain potassium channels TREK-1 and TRAAK. [[KCNQ channels|KCNQ potassium channel family]] are gated by PIP<sub>2</sub>.<ref>{{cite journal | vauthors = Brown DA, Passmore GM | title = Neural KCNQ (Kv7) channels | journal = British Journal of Pharmacology | volume = 156 | issue = 8 | pages = 1185–95 | date = April 2009 | pmid = 19298256 | pmc = 2697739 | doi = 10.1111/j.1476-5381.2009.00111.x }}</ref> The voltage activated potassium channel (Kv) is regulated by PA. Its midpoint of activation shifts +50 mV upon PA hydrolysis, near resting membrane potentials.<ref>{{cite journal | vauthors = Hite RK, Butterwick JA, MacKinnon R | title = Phosphatidic acid modulation of Kv channel voltage sensor function | journal = eLife | volume = 3 | date = October 2014 | pmid = 25285449 | pmc = 4212207 | doi = 10.7554/eLife.04366 | doi-access = free }}</ref> This suggests Kv could be opened by lipid hydrolysis independent of voltage and may qualify this channel as dual lipid and voltage gated channel.