IMR Press / FBS / Volume 8 / Issue 1 / DOI: 10.2741/S454

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Physiological roles of the transient outward current Ito in normal and diseased hearts

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1 Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, New York, 13501 USA
2 Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Dyrlægevej 100, 1870 Frederiksberg C, Denmark
3 Departments of Physiology and Medicine, University Health Network, University of Toronto. 1 King’s College Circle, Toronto, Ontario, M5S 1A8 Canada
4 Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8 Canada

*Author to whom correspondence should be addressed.

Academic Editors: Gerrie Farman, Peter Backx

Front. Biosci. (Schol Ed) 2016, 8(1), 143–159;
Published: 1 January 2016

The Ca2+-independent transient outward K+ current (Ito) plays a critical role in underlying phase 1 of repolarization of the cardiac action potential and, as a result, is central to modulating excitation-contraction coupling and propensity for arrhythmia. Additionally, Ito and its molecular constituents are consistently reduced in cardiac hypertrophy and heart failure. In this review, we discuss the physiological role of Ito as well as the molecular basis of this current in human and canine hearts, in which Ito has been thoroughly studied. In particular, we discuss the role of Ito in the action potential and the mechanisms by which Ito modulates excitation-contraction coupling. We also describe the effects of mutations in the subunits constituting the Ito channel as well as the role of Ito in the failing myocardium. Finally, we review pharmacological modulation of Ito and discuss the evidence supporting the hypothesis that restoration of Ito in the setting of heart failure may be therapeutically beneficial by enhancing excitation-contraction coupling and cardiac function.

Heart Failure
Potassium Channel
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