Reduced calcium current density in single myocytes isolatedfrom hypertrophied failing guinea pig hearts

The present study explored the possibility that an alteration in the transmembrane calcium current (I_Ca), through its ability to modulate Ca²⁺ release from the sarcoplasmic reticulum, could contribute to the depressed peak [Ca²⁺]_i we previously observed in hypertrophied failing myocardium. Whole-cell patch clamp was used to measure I_Ca in single guinea pig ventricular myocytes isolated from hearts of normal guinea pigs andfrom guinea pig hearts in which hypertrophy and failure were induced by gradually developing left ventricular pressure overload subsequent to ascending aortic banding of young animals. Membrane capacitance (C_m) was significantly greater, and I_Ca, normalized for C_m was significantly lower in myocytes from hypertrophied failing hearts. Myocytes from hypertrophied failing hearts did not differ significantly from normal myocytes in terms of the voltage-dependence of the activation variable (d) of I_Ca (except at − 30 mV), the time course of removal of inactivation of I_Ca, and the time constant of decay of I_Ca. Measurement of the voltage dependence of the inactivation variable (f) of I_Ca showed that significantly more steady-state inactivation was present at 0, −10, and −20 mV inmyocytes from hypertrophied failing hearts. Multiple regression analysis of all data indicated that I_Ca density decreased with increasing myocyte membrane area (as reflected by Cm) irrespective of any specific effects of hypertrophy and heart failure. We conclude that I_Ca, normalized for C_m, is significantly reduced in myocytes isolated from hypertrophiedfailing hearts, probably by a process associated with increased cell size, per se.