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Kir6.2 is required for adaptation to stress

2002; National Academy of Sciences; Volume: 99; Issue: 20 Linguagem: Inglês

10.1073/pnas.212315199

1091-6490

Leonid V. Zingman, Denice M. Hodgson, Peter Bast, Garvan C. Kane, Carmen Pérez-Terzic, Richard J. Gumina, Darko Pucar, Martin Bienengraeber, Petras P. Dzeja, Takashi Miki, Susumu Seino, Alexey E. Alekseev, André Terzic,

Cardiac Ischemia and Reperfusion

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.