Roles of KATP channels as metabolic sensors in acute metabolic changes.
Physiological and pathophysiological roles of K(ATP) channels have been clarified recently in genetically engineered mice. The Kir6.2-containing K(ATP) channels in pancreatic ss-cells and the hypothalamus are essential in the regulation of glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and are involved in glucose uptake in skeletal muscles, thus playing a key role in the maintenance of glucose homeostasis. Disruption of Kir6.1-containing K(ATP) channels in mice leads to spontaneous vascular spasm mimicking vasospastic (Prinzmetal) angina in humans, indicating that the Kir6.1-containing K(ATP) channels in vascular smooth muscles participate in the regulation of vascular tonus, especially in coronary arteries. Together with protective roles of K(ATP) channels against cardiac ischemia and hypoxia-induced seizure propagation, it is now clear that K(ATP) channels, as metabolic sensors, are critical in the maintenance of homeostasis against acute metabolic changes.
Miki
Takashi
T
Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Japan.
Seino
Susumu
S
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000788:Angina Pectoris, Variant / Q000188:drug therapy; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism; D005089:Exocytosis; D005934:Glucagon / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009474:Neurons / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011955:Receptors, Drug / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D005934:Glucagon; D005947:Glucose; D007328:Insulin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel