title: Kir6.2 is required for adaptation to stress.
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.
authors.affiliation: Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Leonid V
authors.initials: LV
authors.lastname: Zingman
authors.forename: Denice M
authors.initials: DM
authors.lastname: Hodgson
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bast
authors.forename: Garvan C
authors.initials: GC
authors.lastname: Kane
authors.forename: Carmen
authors.initials: C
authors.lastname: Perez-Terzic
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gumina
authors.forename: Darko
authors.initials: D
authors.lastname: Pucar
authors.forename: Martin
authors.initials: M
authors.lastname: Bienengraeber
authors.forename: Petras P
authors.initials: PP
authors.lastname: Dzeja
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Alexey E
authors.initials: AE
authors.lastname: Alekseev
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D003645:Death, Sudden; D004594:Electrophysiology; D006439:Hemodynamics; D006706:Homeostasis; D007477:Ions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010477:Perfusion; D010805:Physical Conditioning, Animal; D005082:Physical Exertion; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000502:physiology*; D013312:Stress, Physiological; D013997:Time Factors
chemical_list: D007477:Ions; D024661:Potassium Channels, Inwardly Rectifying; D002118:Calcium