ELECTROPHYSIOLOGICAL EFFECTS OF CHANGROLIN, AN ANTIARRHYTHMIC AGENT DERIVED FROM DICHROA-FEBRIFUGA, ON GUINEA-PIG AND RABBIT HEART-CELLS

1. The electrophysiological effects of changrolin (CRL), a Chinese ant i-arrhythmic drug derived from a traditional antimalarial plant, were examined using the whole-cell patch-clamp method on single cells isola ted from guinea-pig and rabbit hearts. 2. At a clinically relevant con centration of 50 mu mol/L changrolin inhibited I-Ca by 19.3+/-6.O% and 17.3+/-2.6% in guinea-pig and rabbit ventricular cells, respectively. The voltage-dependent channel availability curve was not affected. Th e CRL effect was enhanced to a small extent during a repetitive stimul ation at 2 Hz. 3. I-Na was resistant to CRL and the channel availabili ty curve was also unaffected. A small use-dependent inhibition was obs erved only when the I-Na was elicited at 5 Hz in the presence of 300 m u mol/L CRL. 4. At 50 mu mol/L, CRL did not affect the time-independen t inward rectifier and the delayed rectifier K+ currents (I-K1 and I-K , respectively), but inhibited the transient outward current (I-TO) by 17.7+/-2.4%. Changrolin significantly shortened the action potential duration in both guinea-pig and rabbit ventricular cells. 5. In conclu sion, CRL inhibits I-Ca and I-TO but has little effect on I-Na.