Abstract
Marked reductions in the densities of the fast, transient voltage-dependent K(+) (Kv) current, I(to,f), and of the inwardly rectifying (Kir) K(+) current, I(K1), are routinely observed in the hypertrophied and failing human heart and in experimental models of pathological cardiac hypertrophy. Attenuation of these prominent repolarizing K(+) currents results in action potential prolongation and increased dispersion of repolarization, both of which are arrhythmogenic. Cardiac hypertrophy and failure are also associated with increased expression and activity of the multifunctional calcium (Ca(2+)) calmodulin (CaM) dependent protein kinase II (CaMKII) and several lines of evidence suggest that CaMKII activation can (directly or indirectly) lead to changes in the functional cell surface expression and the biophysical properties of cardiac I(to,f) and I(K1) channels.