INHIBITION BY CADMIUM IONS OF THE ELECTRICAL ACTIVITY OF SINOATRIAL NODAL PACEMAKER FIBERS AND THEIR RESPONSE TO NOREPINEPHRINE

¹ Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan

In rabbit sinoatrial (SA) node pacemaker fibers, the overshoot, the maximal diastolic potential and the threshold potential were decreased and the 10% and 90% durations were prolonged by Cd⁺⁺ (0.1 and 0.5 mM). The slope of diastolic depolarization was decreased, which results in bradycardia. In most of preparations exposed to 0.5 mM Cd⁺⁺, pacemaker activities were totally abolished. The inhibitory effects of Cd⁺⁺ were reversed by cysteine in a concentration insufficient to produce changes in the membrane potential of pacemaker fibers exposed to control solutions. Calcium ions (4.4 mM) did not effectively reverse the effects of Cd⁺⁺. Cadmium-induced changes were prevented by cysteine and Ca⁺⁺. The positive chronotropic effect of sympathetic nerve stimulation, norepinephrine and histamine was inhibited by Cd⁺⁺ (0.02 and 0.1 mM). The chronotropic effect of histamine was not influenced by 10^-6M propranolol. The maximum rate increase by norepinephrine (5 x 10^-5M) and histamine (5 x 10^-4M) was markedly attenuated by Cd⁺⁺. Cysteine and Ca⁺⁺ reversed the Cd⁺⁺ effect. From these results, it can be concluded that membrane constituents containing sulfhydryl groups may play an important role in the maintenance of the spontaneous pacemaker activity, associated possibly with the permeability of membranes for Na⁺. It is postulated that Cd⁺⁺ interferes either with the amine-receptor binding or with an increase in the permeability of pacemaker membranes for Na⁺ during diastole thus inducing tachycardia.