POTASSIUM CHANNEL DOWN-REGULATION IN HEART-FAILURE

Prolongation of action potential duration is the most consistent elect rophysiological abnormality in myocardium and myocytes from hypertroph ied and failing hearts. Measurements of currents in myocytes from hype rtrophied and failing hearts indicate that, in most cases, this is due to a decrease in outward potassium currents. If presents a calcium-in dependent transient outward current is usually substantially reduced, but delayed rectifier and inward rectifier currents have also been fou nd to be diminished. There is increasing evidence that potassium curre nt down-regulation contributes significantly to the enhanced lability of the repolarization process in heart failure, predisposing to early after-depolarizations, dispersion of repolarization and ventricular ar rhythmias. The reduction of outward potassium currents may also he inv olved in the enhanced sensitivity of failing myocardium to triggering factors like hypokalemia, ischemia, and antiarrhythmic agents with Cla ss III effects. A thorough understanding of the mechanisms of cardiac excitability and arrhythmogenesis at the cellular and molecular level under normal and pathological conditions will be essential for the dev elopment of new pharmacological strategies to prevent sudden cardiac d eath in heart failure. (C) 1998 Elsevier Science B.V.