Cardiac ATP-sensitive potassium channels and associated channelopathies

Alexey E. Alekseev, Santiago Reyes, Satsuki Yamada, Sungjo Park, D. Kent Arrell, Garvan M Kane, Timothy Mark Olson, Andre Terzic

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

ATP-sensitive K+ (KATP) channels integrate cellular energy signals with membrane electrical activity. Heteromultimers of KCNJ11-encoded inwardly rectifying potassium Kir6.2 channels and ABCC9-encoded ATP-binding cassette SUR2A proteins, sarcolemmal KATP channels are vital in heart energy homeostasis. Knockout of the Kir6.2 pore compromises cardioprotection afforded by ischemic preconditioning, impairs tolerance to sympathetic surge, and aggravates the impact of endurance challenge or hemodynamic load precipitating heart failure under stress. In human cardiovascular medicine, mutations in the regulatory SUR2A subunit have been linked to KATP channelopathy-associated electrical and cardiomyopathic disorders, including syndromes of adrenergic atrial fibrillation and dilated cardiomyopathy with tachycardia. In clinical heart failure, a common polymorphism in the Kir6.2 subunit has been identi fied as a biomarker for impaired performance in stress-test. The Kir6.2 K23 allele, present in over half the population, has been further pinpointed as a risk factor for susceptibility to maladaptive cardiac remodeling in hypertension. Cardiovascular disorders associated with genetic variation in KATP channel genes also include myocardial infarction and ventricular fibrillation. Thus, advances in molecular medicine have enabled a growing understanding of KATP channel function in health and disease, underscoring the impact on individual and public cardiovascular wellness.

Original languageEnglish (US)
Title of host publicationElectrical Diseases of the Heart: Volume 1: Basic Foundations and Primary Electrical Diseases
PublisherSpringer-Verlag London Ltd
Pages245-258
Number of pages14
ISBN (Print)9781447148814, 9781447148807
DOIs
StatePublished - Jan 1 2013

Keywords

  • Arrhythmias
  • Cardiomyopathy
  • Clinical Genetics
  • Genetics of cardiovascular disease
  • Heart Failure

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Alekseev, A. E., Reyes, S., Yamada, S., Park, S., Arrell, D. K., Kane, G. M., Olson, T. M., & Terzic, A. (2013). Cardiac ATP-sensitive potassium channels and associated channelopathies. In Electrical Diseases of the Heart: Volume 1: Basic Foundations and Primary Electrical Diseases (pp. 245-258). Springer-Verlag London Ltd. https://doi.org/10.1007/978-1-4471-4881-4_15