Kir6.2 is required for adaptation to stress

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

Research output: Contribution to journalArticle

247 Citations (Scopus)

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

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KATP Channels
General Adaptation Syndrome
Calcium Channels
Sudden Death
Cardiac Arrhythmias
Ions
Calcium
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Kir6.2 is required for adaptation to stress. / Zingman, Leonid V.; Hodgson, Denice M.; Bast, Peter H.; Kane, Garvan M; Terzic, Carmen M; Gumina, Richard J.; Pucar, Darko; Bienengraeber, Martin; Dzeja, Petras P; Miki, Takashi; Seino, Susumu; Alekseev, Alexey E.; Terzic, Andre.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 20, 01.10.2002, p. 13278-13283.

Research output: Contribution to journalArticle

Zingman, LV, Hodgson, DM, Bast, PH, Kane, GM, Terzic, CM, Gumina, RJ, Pucar, D, Bienengraeber, M, Dzeja, PP, Miki, T, Seino, S, Alekseev, AE & Terzic, A 2002, 'Kir6.2 is required for adaptation to stress', Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 20, pp. 13278-13283. https://doi.org/10.1073/pnas.212315199
Zingman, Leonid V. ; Hodgson, Denice M. ; Bast, Peter H. ; Kane, Garvan M ; Terzic, Carmen M ; Gumina, Richard J. ; Pucar, Darko ; Bienengraeber, Martin ; Dzeja, Petras P ; Miki, Takashi ; Seino, Susumu ; Alekseev, Alexey E. ; Terzic, Andre. / Kir6.2 is required for adaptation to stress. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 20. pp. 13278-13283.
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AB - 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.

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