K+ channels: generating excitement in pancreatic beta-cells.
K+ channels play a key role in cellular physiology by regulating the efflux of K+ ions. They are the most diverse group of ion channel proteins; more than 30 K+ channel genes have been characterized. Regulated by ATP, voltage, and calcium, multiple K+ channels coexist in the beta-cell to regulate membrane potential, cell excitability, and insulin secretion. Recent developments at the molecular level have greatly expanded our understanding of beta-cell K+ channel structure and function, especially in regard to the ATP-sensitive K+ channel, the target for sulfonylurea drugs. Mutations in K+ channel genes underlie diseases as diverse as persistent hyperinsulinemia of infancy, cardiac long QT syndrome, cerebellar degeneration, and certain ataxias. These discoveries have identified new pharmacological targets for possible therapeutic intervention in the treatment of diabetes.
Dukes
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Glaxo Wellcome Research Institute, Research Triangle Park, North Carolina 27709, USA. dukesI@glaxo.com
Philipson
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D018528:ATP-Binding Cassette Transporters; D000818:Animals; D003920:Diabetes Mellitus / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000503:physiopathology; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D017433:Protein Structure, Secondary; D051381:Rats; D011955:Receptors, Drug / Q000502:physiology; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors