The molecular physiology of the cardiac transient outward potassium current (Ito) in normal and diseased myocardium

The Ca2+-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,I-f, and slow I-to, called I-to,I-s. Recent findings suggest that I-to,I-f is formed by assembly of K-v4.2, and/or K-v4.3, alpha pore-forming voltage-gated subunits while I-to,I-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 Ca2+ 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. (C) 2001 Academic Press.