Kir6.2 is required for adaptation to stress

Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13278-83. doi: 10.1073/pnas.212315199. Epub 2002 Sep 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Biological*
  • Animals
  • Arrhythmias, Cardiac / pathology
  • Calcium / metabolism
  • Death, Sudden
  • Electrophysiology
  • Hemodynamics
  • Homeostasis
  • Ions
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardium / metabolism
  • Neurons / metabolism*
  • Perfusion
  • Physical Conditioning, Animal
  • Physical Exertion
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Potassium Channels, Inwardly Rectifying / physiology*
  • Stress, Physiological
  • Time Factors

Substances

  • Ions
  • Potassium Channels, Inwardly Rectifying
  • Calcium