The slow membrane channel as the predominant mediator of the excitation process of the sinoatrial pacemaker cell.

The slow upstroke velocity of the action potential of primary pacemaker cells of the sinoatrial node suggests the slow membrane channel to be involved in the excitation process of these cells. In order to prove this the effect of promotors and inhibitors of the slow membrane channel upon the excitation process of the isolated sinoatrial node of rabbits was studied. 1. The action potentials of primary pacemaker cells had an upstroke velocity of 1.7 +/- 1.1 V/sec and an overshoot of 8.1 +/- 4.6 mV with a threshold potential of -40.1 +/- 4.5 mV. A decrease of the extracellular Ca concentration from 2 mM to 0.2 mM led to reduction of upstroke velocity and overshoot whereas an increase from 2 mM to 4 mM augmented both parameters. But the inward current is not only carried by Ca ions but by Na ions as well, since Na withdrawal diminished upstroke velocity and overshoot. 2. The promotors of the slow inward current, isoproterenol and caffeine, produced a significant increase of upstroke velocity and overshoot. On the other hand, verapamil (1 mg/1) and D 600 (0.4 MG/1) completely blocked the excitation process within 20-25 min. The same effect could be produced by the bivalent cations Ni (1 mM), Co (1 mM), and Mn (1 mM). These organic and inorganic inhibitors exerted their blocking effect without significant changes of the maximal diastolic potential and the threshold potential. 3. In the continued presence of Ni, Co and Mn ions their inhibitory effect could be neutralized nearly completely by isoproterenol (2.5 mg/1). But excess Ca (6 mM) increased the upstroke velocity only to a small degree. In contrast to the findings in the ventricular myocardium the blocking effect of verapamil and D 600 could be overcome neither by isoproterenol nor by excess Ca. The excitation process in the sinotrial node is mediated solely by the slow membrane channel. It allows the influx of both Ca and Na ions which act as charge carrier of the slow inward current. The fact, that the inhibitory effect of verapamil and D 600 cannot be neutralized by catecholamines or excess Ca seems to indicate that some properties of the slow membrane channel are not exactly identical in sinotrial pacemaker cells and in the ventricular myocardium.