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All K<sub>ir</sub> channels require [[phosphatidylinositol 4,5-bisphosphate]] (PIP<sub>2</sub>) for activation.<ref name="pmid18411329">{{cite journal | vauthors = Tucker SJ, Baukrowitz T | title = How highly charged anionic lipids bind and regulate ion channels | journal = The Journal of General Physiology | volume = 131 | issue = 5 | pages = 431–8 | date = May 2008 | pmid = 18411329 | pmc = 2346576 | doi = 10.1085/jgp.200709936 }}</ref> PIP<sub>2</sub> binds to and directly activates K<sub>ir</sub> 2.2 with agonist-like properties.<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> In this regard K<sub>ir</sub> channels are PIP<sub>2</sub> [[ligand-gated ion channels]].
==Role
K<sub>ir</sub> channels are found in multiple cell types, including [[macrophages]], [[cardiac]] and [[kidney]] cells, [[leukocytes]], [[neurons]], and endothelial cells. By mediating a small [[depolarization|depolarizing]] K<sup>+</sup> current at negative membrane potentials, they help establish resting membrane potential, and in the case of the [[G protein-coupled inwardly-rectifying potassium channel|K<sub>ir</sub>3]] group, they help mediate inhibitory [[neurotransmitter]] responses, but their roles in cellular physiology vary across cell types:
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