[3H]Noradrenaline Release from Brain Slices Induced by an Increase in the Intracellular Sodium Concentration: Role of Intracellular Calcium Stores

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Abstract
Rat brain slices, prelabeled with [3H]noradrenaline, were superfused and exposed to K+ depolarization (10‐120 mM K+) or to veratrine (1‐25 μM). In the absence of extracellular Ca2+ veratrine, in contrast to K+‐depolarization, caused a substantial release of [3H]noradrenaline, which was completely blocked by tetrodotoxin (0.3 μM). The Ca2+ antagonist Cd2+ (50 μM), which strongly reduced K+‐induced release in the presence of 1.2 mM Ca2+, did not affect release induced by veratrine in the absence of extracellular Ca2+. Ruthenium red (10 μM), known to inhibit Ca2+‐entry into mitochondria, enhanced veratrine‐induced [3H]noradrenaline release. Compared with K+ depolarization in the presence of 1.2 mM Ca2+, veratrine in the absence of Ca2+ caused a somewhat delayed release of [3H]noradrenaline. Further, in contrast to the fractional release of [3H]noradrenaline induced by continuous K+ depolarization in the presence of 1.2 mM Ca2+, that induced by prolonged veratrine stimulation in the absence of Ca2+ appeared to be more sustained. The data strongly suggest that veratrine‐induced [3H]noradrenaline release in the absence of extracellular Ca2+ is brought about by a mobilization of Ca2+ from intracellular stores, e.g., mitochondria, subsequent to a strongly increased intracellular Na+ concentration. This provides a model for establishing the site of action of drugs that alter the stimulussecretion coupling process in central noradrenergic nerve terminals.