ATP-sensitive potassium channels in physiology, pathophysiology, and pharmacology.
Potassium-selective ion channels, whose activity is inhibited by micromolar to millimolar concentrations of ATP presented at the cytoplasmic ATP-sensitive K+ (K+[ATP]) surface, have been found in a variety of cell types. These "K+(ATP) channels" have emerged as significant targets for physiologic as well as pharmacologic modulation of cell processes. In insulin-secreting beta cells of the pancreatic islet, closure of these channels on presentation of a metabolite secretogogue, such as glucose, or an oral hypoglycemic sulfonylurea, results in cell depolarization and triggers electrical activity. Ultimately, this results in Ca2+ entry and Ca(2+)-dependent exocytosis of insulin granules. In myocytes, opening of K+(ATP) channels during hypoxia or metabolite deprivation or with exposure to a new class of K+ channel opener drugs results in cell hyperpolarization and myocyte relaxation. This contributes to vasodilation. In renal tubule cells, K+(ATP) channels contribute to cell potassium balance during vectorial bulk solute transfer by the proximal tubule as well as net urinary potassium secretion by the distal nephron. Agents that modulate the activity of these K+(ATP) channels in epithelial cells may prove to be useful as K(+)-sparing diuretics. in epithelial cells may prove to be useful as K(+)-sparing diuretics.
Department of Medicine, Washington University Medical Center, St. Louis, MO 63110.
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Misler
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Giebisch
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D015221:Potassium Channels; D000255:Adenosine Triphosphate