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Heart Failure Reviews
Published in: Heart Failure Reviews 3/2015

01-05-2015

Transient outward potassium channel: a heart failure mediator

Authors: Qianwen He, Ying Feng, Yanggan Wang

Published in: Heart Failure Reviews | Issue 3/2015

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Abstract

Transient outward K+ current (I to) plays a crucial role in shaping the early phase of repolarization and setting the plateau voltage level of action potential. As a result, it extensively affects membrane current flow in the plateau window. A great body of evidence illustrates a transmural gradient of I to within ventricular wall with much higher density in epicardial than endocardial myocytes, which is important for the physiological ventricular repolarization. In heart failure (HF), this gradient is diminished due to a greater reduction of I to in epicardial myocytes. This attenuates the transmural gradient of early repolarization, facilitating conduction of abnormal impulses originated in the epicardium. In addition, I to reduction prolongs action potential duration and increases intercellular Ca2+, thus affecting Ca2+ handling and the excitation–contraction coupling. Furthermore, increased intercellular Ca2+ could activate CaMKII and calcineurin whose role in cardiac hypertrophy and HF development has been well established. Based on the impact of I to reduction on electrical activity, signal conduction, calcium handling and cardiac function, restoration of I to is likely a potential therapeutic strategy for HF. In this review, we summarize the physiological and pathological role of cardiac I to channel and the potential impact of I to restoration on HF therapy with an emphasis of recent novel findings.
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Metadata
Title
Transient outward potassium channel: a heart failure mediator
Authors
Qianwen He
Ying Feng
Yanggan Wang
Publication date
01-05-2015
Publisher
Springer US
Published in
Heart Failure Reviews / Issue 3/2015
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-015-9474-y

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