title: Physiological roles of the transient outward current Ito in normal and diseased hearts.
abstract: The Ca(2+)-independent transient outward K(+) current (I(to)) 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, I(to) and its molecular constituents are consistently reduced in cardiac hypertrophy and heart failure. In this review, we discuss the physiological role of I(to) as well as the molecular basis of this current in human and canine hearts, in which I(to) has been thoroughly studied. In particular, we discuss the role of Ito; in the action potential and the mechanisms by which I(to) modulates excitation-contraction coupling. We also describe the effects of mutations in the subunits constituting the Ito channel as well as the role of I(to) in the failing myocardium. Finally, we review pharmacological modulation of I(to) and discuss the evidence supporting the hypothesis that restoration of I(to) in the setting of heart failure may be therapeutically beneficial by enhancing excitation-contraction coupling and cardiac function.
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, New York, 13501 USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cordeiro
authors.affiliation: Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Dyrlægevej 100, 1870 Frederiksberg C, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Calloe
authors.affiliation: Departments of Physiology and Medicine, University Health Network, University of Toronto. 1 King\'s College Circle, Toronto, Ontario, M5S 1A8 Canada.
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Aschar-Sobbi
authors.affiliation: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8 Canada.
authors.forename: Kyoung-Han
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Departments of Physiology and Medicine, University Health Network, University of Toronto. 1 King\'s College Circle, Toronto, Ontario, M5S 1A8 Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Korogyi
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, New York, 13501 USA.
authors.forename: Dona
authors.initials: D
authors.lastname: Occhipinti
authors.affiliation: Departments of Physiology and Medicine, University Health Network, University of Toronto. 1 King\'s College Circle, Toronto, Ontario, M5S 1A8 Canada.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Backx
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, New York, 13501 USA, panamab@mmrl.edu.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Panama
mesh_terms: D000200:Action Potentials; D000818:Animals; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D058990:Molecular Targeted Therapy; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D015221:Potassium Channels