The molecular physiology of the cardiac transient outward potassium current (I(to)) in normal and diseased myocardium.
G. Y. Oudit, Z. Kassiri, R. Sah, R. J. Ramirez, C. Zobel and P. H. Backx. The Molecular Physiology of the Cardiac Transient Outward Potassium Current (I(to)) in Normal and Diseased Myocardium. Journal of Molecular and Cellular Cardiology (2001) 33, 851-872. The Ca(2+)-independent transient outward potassium current (I(to)) plays an important role in early repolarization of the cardiac action potential. I(to)has been clearly demonstrated in myocytes from different cardiac regions and species. Two kinetic variants of cardiac I(to)have been identified: fast I(to), called I(to,f), and slow I(to), called I(to,s). Recent findings suggest that I(to,f)is formed by assembly of K(v4.2)and/or K(v4.3)alpha pore-forming voltage-gated subunits while I(to,s)is comprised of K(v1.4)and possibly K(v1.7)subunits. In addition, several regulatory subunits and pathways modulating the level and biophysical properties of cardiac I(to)have been identified. Experimental findings and data from computer modeling of cardiac action potentials have conclusively established an important physiological role of I(to)in rodents, with its role in large mammals being less well defined due to complex interplay between a multitude of cardiac ionic currents. A central and consistent electrophysiological change in cardiac disease is the reduction in I(to)density with a loss of heterogeneity of I(to)expression and associated action potential prolongation. Alterations of I(to)in rodent cardiac disease have been linked to repolarization abnormalities and alterations in intracellular Ca(2+)homeostasis, while in larger mammals the link with functional changes is far less certain. We review the current literature on the molecular basis for cardiac I(to)and the functional consequences of changes in I(to)that occur in cardiovascular disease.
Oudit
G Y
GY
Department of Medicine and Physiology, Toronto General Hospital, 101 College Street, Toronto, M5G 2C4, Canada.
Kassiri
Z
Z
Sah
R
R
Ramirez
R J
RJ
Zobel
C
C
Backx
P H
PH
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D015536:Down-Regulation; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D013997:Time Factors
D015221:Potassium Channels; D002118:Calcium