DEPENDENCE OF HEMICHOLINIUM ACTION ON CALCIUM CONCENTRATION

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

The hypothesis that the action of hemicholinium (HC-3) is directly dependent on the extracellular Ca concentration Was tested in the spontaneously beating right atrial preparation of the rabbit. The negative chronotropic response following electrical stimulation of intrasinoatrial node vagal fibers (cholinergic electrorelease response, or CERR) was used to test the antagonistic action of HC-3. Hemicholinium was applied in nutrient solution containing Ca concentrations ranging from 0.1 to 10.0 mM. The amount of cholinergic blockade by HC-3 was a direct function of the Ca concentration. The amount of blockade was also directly correlated with the magnitude of the negative chronotropic response to vagal stimulation. On the assumption that the magnitude of the CERR was proportional to the release of acetylchohne (ACh), the relationship was interpreted to illustrate that depletion of presynaptic stores of ACh underlies the cholinergic blockade produced by HC-3.