Inhibitory Effect of Cinobufagin on L-Type Ca(2+) Currents, Contractility, and Ca(2+) Homeostasis of Isolated Adult Rat Ventricular Myocytes

Cinobufagin (CBG), a major bioactive ingredient of the bufanolide steroid compounds of Chan Su, has been widely used to treat coronary heart disease. At present, the effect of CBG on the L-type Ca(2+) current (I (Ca-L)) of ventricular myocytes remains undefined. The aim of the present study was to characterize the effect of CBG on intracellular Ca(2+) ([Ca(2+)](i)) handling and cell contractility in rat ventricular myocytes. CBG was investigated by determining its influence on I (Ca-L), Ca(2+) transient, and contractility in rat ventricular myocytes using the whole-cell patch-clamp technique and video-based edge-detection and dual-excitation fluorescence photomultiplier systems. The dose of CBG (10(−8) M) decreased the maximal inhibition of CBG by 47.93%. CBG reduced I (Ca-L) in a concentration-dependent manner with an IC(50) of 4 × 10(−10) M, upshifted the current-voltage curve of I (Ca-L), and shifted the activation and inactivation curves of I (Ca-L) leftward. Moreover, CBG diminished the amplitude of the cell shortening and Ca(2+) transients with a decrease in the time to peak (Tp) and the time to 50% of the baseline (Tr). CBG inhibited L-type Ca(2+) channels, and reduced [Ca(2+)](i) and contractility in adult rat ventricular myocytes. These findings contribute to the understanding of the cardioprotective efficacy of CBG.