Kir6.2 is required for adaptation to stress

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

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251 Scopus citations

Abstract

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 (KATP) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted KATP 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 KATP channels in the heart.

Original languageEnglish (US)
Pages (from-to)13278-13283
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number20
DOIs
StatePublished - Oct 1 2002

ASJC Scopus subject areas

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    Zingman, L. V., Hodgson, D. M., Bast, P. H., Kane, G. C., Perez-Terzic, C., Gumina, R. J., Pucar, D., Bienengraeber, M., Dzeja, P. P., Miki, T., Seino, S., Alekseev, A. E., & Terzic, A. (2002). Kir6.2 is required for adaptation to stress. Proceedings of the National Academy of Sciences of the United States of America, 99(20), 13278-13283. https://doi.org/10.1073/pnas.212315199