ELECTROPHYSIOLOGICAL MECHANISMS FOR THE ANTIARRHYTHMIC ACTION OF (-)-CARYACHINE IN RAT-HEART

(-)-Caryachine (CNMe) is a pavine derivative, isolated from Crytocarya chinensis Hemsl. We wished to illustrate the electrophysiological eff ect and antiarrhythmic potential of this compound on rat cardiac tissu es. Action potential and ionic currents in single ventricular cells we re examined by current clamp or voltage clamp in a whole-cell configur ation. CNMe concentration-dependently suppressed the maximum rate of r ise of the action potential upstroke (V-max) and prolonged the action potential duration at 50% of repolarization (APD(50)). A voltage-clamp study showed that the suppression of V-max by CNMe was associated wit h an inhibition of sodium inward current (I-Na, IC50 = 4.1 mu M). The prolongation of APD(50) was associated with an inhibition of transient outward current (I-to, IC50 = 16.1 mu M) CNMe reduced the I-Na with a negative shift of its voltage-dependent steady-state inactivation cur ves and slowing of its recovery from inactivation. The use-dependent i nhibition of I-Na by CNMe was enhanced at a higher stimulation rate or at a longer prepulse duration. The fraction of fast recovery of I-Na was reduced, bur the recovery time constant of fast recovery component remained unaffected. The inhibition of I-to by CNMe (10-30 mu M) was associated with an acceleration of its time constant of inactivation. According to the analysis of the rime course of inhibition of I-to, CN Me inhibited I-Na in a time-dependent manner. In isolated heart, CNMe could effectively inhibit ischrmia/reperfusion-induced ventricular tac hycardia with an EC(50) of 3.9 mu M. The results indicate that CNMe is a strong I-Na blocker with some I-Na blocking activity. The inhibitio n of I-NA and I-Na may contribute to its antiarrhythmic activity again st ischemia/reperfusion arrhythmia.