The inward rectifier potassium (Kir) channel family is made up of 16 genes (KCNJx) encoding seven sub-families (Kir1–Kir7) of structurally related protein subunits. Kir channels are tetramers of identical (homomeric) or different (heteromeric) subunits, each possessing two transmembrane domains (M1 and M2), a pore loop, and a large cytoplasmic domain. The term ‘inward rectification’ refers to their preference for passing K+ current in the inward direction due to pore block of outward current by intracellular polyamines. Kir channels are pivotal regulators of electrical excitability in neurons and cardiomyocytes and mediate K+ transport in epithelial cells of the kidney tubule. Their importance in humans is underscored by the existence of rare, monogenic diseases caused by mutations in Kir channel-encoding genes. With the emergence of enabling technologies for Kir channel-directed drug discovery in pharmaceutical and academic laboratories, an important and timely question is whether Kir channels represent viable drug targets for these rare ‘channelopathies’.
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