Effects of KW-3049, a newly developed calcium antagonist, on rabbit sinus nodes and guinea pig ventricular muscles.

Abstract

The effects of KW-3049, a newly developed dihydropyridine-type calcium antagonist, were studied on the electrophysiological properties of isolated rabbit sinus node tissues and guinea pig ventricular muscles. In spontaneously firing sinus node pacemaker cells, KW-3049 (greater than or equal to 10(-8) M) prolonged the cycle length, and decreased the maximum upstroke velocity (Vmax) and overshoot (OS) of action potential. KW-3049 (greater than or equal to 10(-6) M) produced a shortening of action potential duration (APD) of normally polarized ventricular muscles without affecting other parameters. Vmax, OS, and APD of slow action potentials, which had been induced by isoproterenol or by barium in K+-depolarized ventricular muscles, were reduced dose-dependently by KW-3049 (greater than 10(-9) M). The relative potency of KW-3049 for the Vmax inhibition of slow responses was 20 times higher than verapamil, but 0.32 times less than nifedipine. In voltage calmp experiments on ventricular muscles, KW-3049 (10(-6) M) caused a decrease of slow inward current by 52.7%, but did not affect the net outward current. These findings suggest that KW-3049 may have a potent and highly selective inhibitory action on cardiac slow channels.