MODIFICATION BY CALCIUM OF THE RELEASE OF AUTONOMIC MEDIATORS IN THE ISOLATED SINOATRIAL NODE

¹ Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington

Effects of Ca ranging from 0.11 to 11.0 mM were studied on the steady state beat interval and on the cholinergic and adrenergic responses to intranodal nerve stimulation in isolated SA node-right atrial preparations. The cholinergic negative chronotropic response to intranodal nerve stimulation was directly proportional to the Ca concentration.

The sensitivity of the SA node did not display a similar proportionality. These observations provide evidence that the excitation-induced release of ACh from vagal endings in the SA node is proportional to the extracellular Ca concentration.

The adrenergic positive chronotropic response to intranodal nerve stimulation was only slightly affected by the Ca concentration.

Calcium exerted a biphasic effect on the steady state beat interval. Between 0.11 and 1.1 mM, increasing Ca produced an increase in beat interval (decrease in spontaneous rate). From 1.1 to 11.0 mM, increasing Ca produced a decrease in beat interval (increase in spontaneous rate). The effects of Ca on the steady state beat interval of untreated, reserpinized, atropinized, and reserpinized-atropinized preparations are consistent with the interpretation that the chronotropic actions of Ca are the result of interaction of direct actions on pacemaker fibers and indirect actions on pacemaker fibers via effects on spontaneous autonomic mediator release.