Boosting the signal: Endothelial inward rectifier K+ channels

Endothelial cells express a diverse array of ion channels including members of the strong inward rectifier family composed of K(IR)2 subunits. These two-membrane 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+ channel (K-IR) currents display a region of negative slope conductance at membrane potentials positive to the K+ equilibrium potential that allows outward current through the channels to be activated by membrane hyperpolarization, permitting K-IR to amplify hyperpolarization induced by other K+ channels and ion transporters. Increases in extracellular K+ concentration activate K-IR allowing them to sense extracellular K+ concentration and transduce this change into membrane hyperpolarization. These properties position K-IR to participate in the mechanism of action of hyperpolarizing vasodilators and contribute to cell-cell conduction of hyperpolarization along the wall of microvessels. The expression of K-IR in capillaries in electrically active tissues may allow K-IR to sense extracellular K+, contributing to functional hyperemia. Understanding the regulation of expression and function of microvascular endothelial K-IR 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.