title: Role of ATP-sensitive K+ channels in cardiac arrhythmias.
abstract: The sarcolemmal adenosine triphosphate (ATP)-sensitive K(+) (sarcKATP) channel in the heart is a hetero-octamer comprising the pore-forming subunit Kir6.2 and the regulatory subunit sulfonylurea receptor SUR2A. By functional analysis of genetically engineered mice lacking sarcKATP channels, the pathophysiological roles of the K(+) channel in the heart have been extensively evaluated. Although mitochondrial KATP (mitoKATP) channel is proposed to be an important effector for the protection of ischemic myocardium and the inhibition of ischemia/reperfusion-induced ventricular arrhythmias, the molecular identity of mitoKATP channel has not been established. Although selective sarcKATP-channel blockers can prevent ischemia/reperfusion-induced ventricular arrhythmias by inhibiting the action potential shortening in the acute phase, the drugs may aggravate the ischemic damages due to intracellular Ca(2+) overload. The sarcKATP channel is also mandatory for optimal adaptation to hemodynamic stress such as sympathetic activation. Dysfunction of mutated sarcKATP channels in atrial cells may lead to electrical instability and atrial fibrillation. Recently, it has been proposed that the gain-of-function mutation of cardiac Kir6.1 channel can be a pathogenic substrate for J wave syndromes, a cause of idiopathic ventricular fibrillation as early repolarization syndrome or Brugada syndrome, whereas loss of function of the channel mutations can underlie sudden infant death syndrome. However, precise role of Kir6.1 channels in cardiac cells remains to be defined and further study may be needed to clarify the role of Kir6.1 channel in the heart.
authors.affiliation: 1Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Haruaki
authors.initials: H
authors.lastname: Nakaya
mesh_terms: D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D015444:Exercise / Q000502:physiology; D006801:Humans; D054086:KATP Channels / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology*; D012508:Sarcolemma / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel; C117780:mitochondrial K(ATP) channel; C092520:uK-ATP-1 potassium channel
keywords: ATP-sensitive K+ channel; J wave syndrome; Kir6.1; Kir6.2