Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci U S A 2002 Oct 01;99(20):13278-83
Date
09/25/2002Pubmed ID
12271142Pubmed Central ID
PMC130624DOI
10.1073/pnas.212315199Scopus ID
2-s2.0-0036789964 (requires institutional sign-in at Scopus site) 271 CitationsAbstract
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.
Author List
Zingman LV, Hodgson DM, Bast PH, Kane GC, Perez-Terzic C, Gumina RJ, Pucar D, Bienengraeber M, Dzeja PP, Miki T, Seino S, Alekseev AE, Terzic AMESH terms used to index this publication - Major topics in bold
Adaptation, BiologicalAnimals
Arrhythmias, Cardiac
Calcium
Death, Sudden
Electrophysiology
Hemodynamics
Homeostasis
Ions
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium
Neurons
Perfusion
Physical Conditioning, Animal
Physical Exertion
Potassium Channels, Inwardly Rectifying
Stress, Physiological
Time Factors
