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.