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J Physiol. 2017 Apr 1;595(7):2209-2228. doi: 10.1113/JP272864. Epub 2016 Nov 13.

Potassium channels in the heart: structure, function and regulation.

Author information

1
Department of Pharmacology, University of California, Davis, Davis, CA, 95616, USA.
2
Department of Internal Medicine, University of Utah, Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, UT, 84112, USA.
3
Department of Internal Medicine, Division of Cardiology, University of California, Davis, CA, 95616, USA.
4
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, 10032, USA.
5
Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA.
6
Department of Cardiology, Cardiovascular Research Institute Maastricht, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands.
7
Centre for Molecular Simulation, Department of Biological Sciences, University of Calgary, Calgary, AB, T2N 1N4, Canada.
8
Department of Physiology and Biophysics, University of Colorado - Anschutz Medical Campus, Denver, CO, 80045, USA.
9
Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.
10
Department of Physiology and Membrane Biology, University of California, Davis, CA, 95616, USA.

Abstract

This paper is the outcome of the fourth UC Davis Systems Approach to Understanding Cardiac Excitation-Contraction Coupling and Arrhythmias Symposium, a biannual event that aims to bring together leading experts in subfields of cardiovascular biomedicine to focus on topics of importance to the field. The theme of the 2016 symposium was 'K+ Channels and Regulation'. Experts in the field contributed their experimental and mathematical modelling perspectives and discussed emerging questions, controversies and challenges on the topic of cardiac K+ channels. This paper summarizes the topics of formal presentations and informal discussions from the symposium on the structural basis of voltage-gated K+ channel function, as well as the mechanisms involved in regulation of K+ channel gating, expression and membrane localization. Given the critical role for K+ channels in determining the rate of cardiac repolarization, it is hardly surprising that essentially every aspect of K+ channel function is exquisitely regulated in cardiac myocytes. This regulation is complex and highly interrelated to other aspects of myocardial function. K+ channel regulatory mechanisms alter, and are altered by, physiological challenges, pathophysiological conditions, and pharmacological agents. An accompanying paper focuses on the integrative role of K+ channels in cardiac electrophysiology, i.e. how K+ currents shape the cardiac action potential, and how their dysfunction can lead to arrhythmias, and discusses K+ channel-based therapeutics. A fundamental understanding of K+ channel regulatory mechanisms and disease processes is fundamental to reveal new targets for human therapy.

KEYWORDS:

gating; heterogeneity; phosphorylation; trafficking

PMID:
27861921
PMCID:
PMC5374109
DOI:
10.1113/JP272864
[Indexed for MEDLINE]
Free PMC Article

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