Channelopathies of inwardly rectifying potassium channels

Mutations in genes encoding ion channels have increasingly been identified to cause disease conditions collectively termed channelopathies. Recognizin g the molecular basis of an ion channel disease has provided new opportunit ies for screening, early diagnosis, and therapy of such conditions. This sy nopsis provides an overview of progress in the identification of molecular defects in inwardly rectifying potassium (Kir) channels. Structurally and f unctionally distinct from other channel families, Kir channels are ubiquito usly expressed and serve functions as diverse as regulation of resting memb rane potential, maintenance of K+ homeostasis, control of heart rate, and h ormone secretion. In humans, persistent hyperinsulinemic hypoglycemia of in fancy, a disorder affecting the function of pancreatic beta cells, and Bart ter's syndrome, characterized by hypokalemic alkalosis, hypercalciuria, inc reased serum aldosterone, and plasma renin activity, are the two major dise ases Linked so far to mutations in a Kir channel or associated protein. In addition, the weaver phenotype, a neurological disorder in mice, has also b een associated with mutations in a Kir channel subtype. Further genetic lin kage analysis and full understanding of the consequence that a defect in a Kir channel would have on disease pathogenesis are among the priorities in this emerging field of molecular medicine.-Abraham, M. R., Jahangir, A., Al ekseev, A. E., Terzic, A. Channelopathies of inwardly rectifying potassium channels.