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These two\u2010membrane spanning domain channels are modulated by their lipid environment, and exist in macromolecular signaling complexes with receptors, protein kinases and other ion channels. Inward rectifier K<jats:sup>+<\/jats:sup> channel (K<jats:sub>IR<\/jats:sub>) currents display a region of negative slope conductance at membrane potentials positive to the K<jats:sup>+<\/jats:sup> equilibrium potential that allows outward current through the channels to be activated by membrane hyperpolarization, permitting K<jats:sub>IR<\/jats:sub> to amplify hyperpolarization induced by other K<jats:sup>+<\/jats:sup> channels and ion transporters. Increases in extracellular K<jats:sup>+<\/jats:sup> concentration activate K<jats:sub>IR<\/jats:sub> allowing them to sense extracellular K<jats:sup>+<\/jats:sup> concentration and transduce this change into membrane hyperpolarization. These properties position K<jats:sub>IR<\/jats:sub> to participate in the mechanism of action of hyperpolarizing vasodilators and contribute to cell\u2010cell conduction of hyperpolarization along the wall of microvessels. The expression of K<jats:sub>IR<\/jats:sub> in capillaries in electrically active tissues may allow K<jats:sub>IR<\/jats:sub> to sense extracellular K<jats:sup>+<\/jats:sup>, contributing to functional hyperemia. Understanding the regulation of expression and function of microvascular endothelial K<jats:sub>IR<\/jats:sub> will improve our understanding of the control of blood flow in the microcirculation in health and disease and may provide new targets for the development of therapeutics in the future.<\/jats:p>","DOI":"10.1111\/micc.12319","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T16:16:39Z","timestamp":1474474599000},"source":"Crossref","is-referenced-by-count":40,"title":["Boosting the signal: Endothelial inward rectifier K<sup>+<\/sup> channels"],"prefix":"10.1111","volume":"24","author":[{"given":"William F.","family":"Jackson","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Michigan State University  East Lansing MI 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