Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (I(to)).
The cardiac action potential (AP) is critical for initiating and coordinating myocyte contraction. In particular, the early repolarization period of the AP (phase 1) strongly influences the time course and magnitude of the whole-cell intracellular Ca(2+) transient by modulating trans-sarcolemmal Ca(2+) influx through L-type Ca(2+) channels (I(Ca,L)) and Na-Ca exchangers (I(Ca,NCX)). The transient outward potassium current (I(to)) has kinetic properties that make it especially effective in modulating the trajectory of phase 1 repolarization and thereby cardiac excitation-contraction coupling (ECC). The magnitude of I(to) varies greatly during cardiac development, between different regions of the heart, and is invariably reduced as a result of heart disease, leading to corresponding variations in ECC. In this article, we review evidence supporting a modulatory role of I(to) in ECC through its influence on I(Ca,L), and possibly I(Ca,NCX). We also discuss differential effects of I(to) on ECC between different species, between different regions of the heart and in heart disease.
Sah
Rajan
R
Department of Physiology, University of Toronto, Heart & Stroke/Richard Lewar Centre, Room 68, Fitzgerald Building, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
Ramirez
Rafael J
RJ
Oudit
Gavin Y
GY
Gidrewicz
Dominica
D
Trivieri
Maria G
MG
Zobel
Carsten
C
Backx
Peter H
PH
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015221:Potassium Channels; D002118:Calcium