EFFECT OF A NOVEL CLASS-I ANTIARRHYTHMIC AGENT, TYB-3823, ON THE CALCIUM CURRENT IN SINGLE GUINEA-PIG VENTRICULAR MYOCYTES

The effect of TYB-3823 on Ca2+ current (I(Ca)) of guinea pig ventricular myocytes was investigated by means of whole-cell patch-clamp technique. TYB-3823 (100-1,000-mu-M) caused a concentration-dependent decrease in I(Ca). Furthermore, a reduction of I(Ca) induced by TYB-3823 (1,000-mu-M) was progressively accentuated by repetitive membrane depolarization, indicating a rate-dependent block of I(Ca). However, the inhibitory potency on I(Ca) was approximately 1/1000 of a Ca2+ antagonistic agent, verapamil hydrochloride. Considering evidence that 3-30-mu-M TYB-3823 decreased the maximum upstroke velocity of the action potential of guinea pig ventricular muscles, it is indicated that the drug does not show its Ca2+ antagonistic property in the usual concentration range as a class I antiarrhythmic agent.