Kir6.2 is required for adaptation to stress.

Zingman LV, Hodgson DM, Bast PH, Kane GC, Perez-Terzic C, Gumina RJ, Pucar D, Bienengraeber M, Dzeja PP, Miki T, Seino S, Alekseev AE, Terzic A
Proc Natl Acad Sci U S A. 2002 99 (20): 13278-83

PMID: 12271142 · PMCID: PMC130624 · DOI:10.1073/pnas.212315199

Reaction to stress requires feedback adaptation of cellular functions to secure a response without distress, but the molecular order of this process is only partially understood. Here, we report a previously unrecognized regulatory element in the general adaptation syndrome. Kir6.2, the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted K(ATP) channel-dependent adjustment of membrane excitability and calcium handling, compromising the enhancement of cardiac performance driven by sympathetic stimulation, a key mediator of the adaptation response. In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart.

MeSH Terms (21)

Adaptation, Biological Animals Arrhythmias, Cardiac Calcium Death, Sudden Electrophysiology Hemodynamics Homeostasis Ions Male Mice Mice, Inbred C57BL Mice, Knockout Myocardium Neurons Perfusion Physical Conditioning, Animal Physical Exertion Potassium Channels, Inwardly Rectifying Stress, Physiological Time Factors

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