ENHANCED FUNCTIONAL EXPRESSION OF TRANSIENT OUTWARD CURRENT IN HYPERTROPHIED FELINE MYOCYTES

Cardiac hypertrophy can decrease myocardial contractility and alter th e electrophysiological activity of the heart. It is well documented th at action potentials recorded from hypertrophied feline ventricular ce lls can exhibit depressed plateau voltages and prolonged durations. Si milar findings have been made by others in rabbit, rat, guinea pig, an d human heart. Whole-cell patch voltage-clamp studies designed to expl ain these changes in the action potential suggest that the only compon ent of the membrane current recorded from feline right ventricular (RV ) myocytes found to be substantially different from normal is the 4-am inopyridine-sensitive transient outward current (I(to)). However. it w as not clear if the change in I(to) could explain the changes in the a ction potential of hypertrophied cardiocytes, nor was it clear if thes e changes reflect an alteration in the electrophysiological character of the channels underlying I(to). A kinetic comparison of I(to) elicit ed by hypertrophied RV myocytes with that elicited by comparable norma l RV myocytes previously revealed no differences, suggesting that the increased magnitude of the peak I(to) recorded from hypertrophied myoc ytes arises because the current density increases and not because of a ny alteration in the kinetic parameters governing the current. This fi nding suggests that in hypertrophy additional normal channels are expr essed rather than a kinetically different channel subtype emerging. In vestigations designed to determine if enhancement of I(to) could expla in the.hypertrophy-induced changes in plateau voltage and action poten tial duration suggest that a change in I(to) density can indeed explai n the entire effect of hypertrophy on RV action potentials. If this no tion is correct, the likelihood of ''sudden death'' in patients with m yocardial hypertrophy might be decreased by a blocker selective for ca rdiac I(to).