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Kir6.2 is required for adaptation to stress

Authors
  • 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
Publisher
The National Academy of Sciences
Publication Date
Sep 23, 2002
Source
PMC
Keywords
Disciplines
  • Biology
License
Unknown

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.

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