Referenced in: none

Automatically associated channels: Kir6.2

Title: 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

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2002 Oct 1 , 99, 13278-83

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12271142

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.