Characteristics of single Ca2+channel kinetics in feline hypertrophied ventricular myocytes

Objective To explore the mechanism underlying the prolongation of action potential and del ayed inactivation of the L-type Ca(2+)(I(Ca),L) current in a feline mo del of left ventricular system hypertension and concomitant hypertrophy. Methods Single Ca(2+)channel properties in myocytes isolated from normal and pressu re overloaded cat left ventricles were studied, using patch-clamp techniques. Left ventricular pressure overload was induced by partial ligation of the ascend ing aorta for 4-6 weeks.Results The amplitude of single Ca(2+)channel current evoked by depolarizing pulses from -40mV to 0mVwas 1.02±0.03pA in normal cells and 1.05±0.03 pA in hypertrophied cells, and there was no difference in single channel current- voltage relationships between the groups since slope conductance was 26.2±1.0 pS in normal and hypertrophied cells, respectively. Peak amplitudes of the en semble-averaged single Ca(2+)channel currents were not different between t he two groups of cells. However, the amplitude of this averaged current at the end of the clamp pulse was significantly larger in hypertrophied cells than in n ormal cells. Open-time histograms revealed that open-time distribution was fi tted by a single exponential function in channels of normal cells and by a two e xponential function in channels of hypertrophied cells. The number of long-las ting openings was increased in channels of hypertrophied cells, and therefore th e calculated mean open time of the channel was significantly longer compared to normal controls. Conclusion Kinetic changes in the Ca(2+)channel may underlie both hypertrophy-associa ted delayed inactivation of the Ca(2+)current and, in part, the pressure ov erload-induced action potential lengthening in this cat model of ventricular le ft systolic hypertension and hypertrophy.