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Cardiac ATP-Sensitive Potassium Channels and Associated Channelopathies

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Electrical Diseases of the Heart

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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 identified 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.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Mayo Clinic, Stabile 5, 200 First Street SW, Rochester, MN, 55905, USA

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

Authors
  1. Alexey E. Alekseev PhD
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  2. Santiago Reyes PhD
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  3. Satsuki Yamada MD, PhD
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  4. Sungjo Park PhD
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  5. D. Kent Arrell PhD
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  6. Garvan C. Kane MD, PhD
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  7. Timothy M. Olson MD
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  8. Andre Terzic MD, PhD
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Corresponding author

Correspondence to Andre Terzic MD, PhD .

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Editors and Affiliations

  1. , Department of Internal Medicine, UMDNJ-RWJ Medical School, Robert Wood Johnson Pl. 1, New Brunswick, 08903-0019, New Jersey, USA

    Ihor Gussak

  2. , Gordon K. Moe Scholar, Masonic Medical Research Laboratory, Bleecker Street, Utica, 13501-1787, New York, USA

    Charles Antzelevitch

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Alekseev, A.E. et al. (2013). Cardiac ATP-Sensitive Potassium Channels and Associated Channelopathies. In: Gussak, I., Antzelevitch, C. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-4471-4881-4_15

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  • DOI: https://doi.org/10.1007/978-1-4471-4881-4_15

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