Cardiac glycosides, calcium and the release of neurotransmitter from peripheral noradrenergic nerves

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Abstract
The requirement for external Ca (Cao) of neurotransmitter release evoked by cardenolides has been investigated in canine saphenous vein. Basal efflux of3H-compounds from saphenous veins pre-loaded with3H-noradrenaline was the same in the absence as in the presence of Cao; Cao is not required for basal efflux of neurotransmitter. Efflux of3H-compounds was increased by cardenolides. Both ACS and ouabain caused a similar maximum net efflux of3H suggesting that each evokes release from the same pool of3H compounds. The similarity of the effects obtained with cardenolides to those obtained during exposure of saphenous vein preparations to potassium-free media suggests that3H-efflux is the result of Na, K-ATPase inhibition. With ACS (ca. EC50) the net efflux of3H-compounds early (o than in its presence whereas at longer times the reverse was true; net efflux was less in the absence of Cao than in its presence. The difference in the3H-efflux pattern was paralleled qualitatively throughout by efflux of3H-noradrenaline. The ACS-evoked efflux of3H-compounds in the presence and absence of Cao derives from sympathetic, noradrenergic nerves;3H present in extraneuronal tissues was not released by the cardenolide. With ouabain (EC50): the total efflux of3H was less in the absence of Cao than in its presence. In the presence of Cao the Ca-channel blocker VP reduced the total3H-efflux evoked by ouabain (>EC50), but did not reduce that evoked by ouabain (50). It is concluded that cardenolide evoked neurotransmitter efflux resulting from Na,K-ATPase inhibition is not dependent upon Cao although its presence, and subsequent entry via VP sensitive channels, does increase the magnitude of the efflux caused by higher concentrations of cardenolides. Whether a component of that efflux evoked by lower concentrations of cardenolides, (or higher concentrations over short time periods) depends on internal Ca stores or is independent of the cation, is not yet clear.