Journal article
Kir6.2 is required for adaptation to stress
Proceedings of the National Academy of Sciences - PNAS, Vol.99(20), pp.13278-13283
10/01/2002
DOI: 10.1073/pnas.212315199
PMCID: PMC130624
PMID: 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.
Details
- Title: Subtitle
- Kir6.2 is required for adaptation to stress
- Creators
- Leonid V Zingman - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsDenice M Hodgson - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsPeter H Bast - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsGarvan C Kane - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsCarmen Perez-Terzic - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsRichard J Gumina - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsDarko Pucar - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsMartin Bienengraeber - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsPetras P Dzeja - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsTakashi Miki - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsSusumu Seino - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsAlexey E Alekseev - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental TherapeuticsAndre Terzic - Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.99(20), pp.13278-13283
- DOI
- 10.1073/pnas.212315199
- PMID
- 12271142
- PMCID
- PMC130624
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 10/01/2002
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094568802771
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