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Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13278-83. Epub 2002 Sep 23.

Kir6.2 is required for adaptation to stress.

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1
Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.

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 (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.

PMID:
12271142
PMCID:
PMC130624
DOI:
10.1073/pnas.212315199
[Indexed for MEDLINE]
Free PMC Article
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