Abstract
Transmembrane potentials were recorded from pacemaker cells of the isolated rabbit sinoatrial node. Following exposure to Ca++ -free media, the pacemaker rate was accelerated, and the maximal diastolic potential, threshold potential and overshoot were decreased. Increase in the gradient of diastolic depolarization by norepinephrine and dibutyryl cyclic AMP was diminished by removal of Ca++ from bathing media. The positive chronotropic effect of norepinephrine was markedly attenuated by removal of Ca++, as was the effect of theophylline and dibutyryl cyclic AMP, which was not significantly influenced by propranolol. Verapamil (2×10-7 to 10-6 M) inhibited the excitatory effect of norepinephrine and theophylline on the slope of diastolic depolarization and pacemaker rate. Treatment with Mn++ (0.3 to I mM) shifted the dose-chronotropic response curve of norepinephrine to the right and downward. On the other hand, lowering external Na+ to 103 or 74 mM by replacing with choline chloride potentiated the positive chronotropic effect of norepinephrine and theophylline. The addition of norepinephrine increased the rate and magnitude of subthreshold oscillations induced in sinoatrial nodal cells by exposure to solutions containing low Na+ and high Ca++. It appears that norepinephrine increases the permeability of Ca++, but not Na+, in pacemaker cells during diastole, resulting in a tachycardia. This increment in the Ca++ permeability may be associated with the increased production of cellular cyclic AMP.
