TY - JOUR
T1 - Physiological roles of the transient outward current Ito in normal and diseased hearts
AU - Cordeiro, Jonathan M.
AU - Callø, Kirstine
AU - Aschar-Sobbi, Roozbeh
AU - Kim, Kyoung-Han
AU - Korogyi, Adam
AU - Occhipinti, Dona
AU - Backx, Peter H.
AU - Panama, Brian K.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
U2 - 10.2741/S454
DO - 10.2741/S454
M3 - Journal article
C2 - 26709904
SN - 1945-0516
VL - 8
SP - 143
EP - 159
JO - Frontiers in bioscience (Scholar edition)
JF - Frontiers in bioscience (Scholar edition)
M1 - 454
ER -