Molecular biology of K(ATP) channels and implications for health and disease.
The ATP-sensitive potassium (K(ATP)) channel is expressed in most excitable tissues and plays a critical role in numerous physiological processes by coupling intracellular energetics to electrical activity. The channel is comprised of four Kir6.x subunits associated with four regulatory sulfonylurea receptors (SUR). Intracellular ATP acts on Kir6.x to inhibit channel activity, while MgADP stimulates channel activity through SUR. Changes in the cytosolic [ATP] to [ADP] ratio thus determine channel activity. Multiple mutations in Kir6.x and SUR genes have implicated K(ATP) channels in various diseases ranging from diabetes and hyperinsulinism to cardiac arrhythmias and cardiovascular disease. Continuing studies of channel physiology and pathology will bring new insights to the molecular basis of K(ATP) channel function, leading to a better understanding of the role that K(ATP) channels play in both health and disease.
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Alejandro
A
Akrouh
S Eliza
SE
Halcomb
Colin G
CG
Nichols
Monica
M
Sala-Rabanal
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000244:Adenosine Diphosphate / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics; D004194:Disease; D006262:Health; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics; D054086:KATP Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008967:Molecular Biology; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate