Role of calcium in synaptosomal substrate oxidation.

The effect of veratridine-mediated depolarization on rat brain synaptosomal respiration in the presence and absence of calcium was investigated. Studies on respiration were performed employing three different pretreatments of the synaptosomes which attempted to deplete endogenous substrates. First, synaptosomes were preincubated for 10 min in the absence of any substrates in medium either containing or devoid of calcium. Second, synaptosomes were preincubated for either 15 or 60-min periods in the presence and absence of calcium, and the incubation medium was changed by centrifugation and resuspension of synaptosomes in their respective media. Irrespective of the prior treatment, maximal stimulation of respiration (400-600%) during veratridine (100 microM) elicited depolarization was observed only when calcium was present in the incubation media. In incubations performed in the absence of calcium, veratridine addition either modestly stimulated (10- and 15-min preincubated synaptosomes) or did not affect (60-min preincubated synaptosomes) the rate of respiration. However, when calcium was added back to these incubations the rate of respiration in the presence of veratridine was stimulated by five- to six-fold. Similarly, the rates of 14CO2 production from [1-14C]- and [2-14C]pyruvate were increased by veratridine only when synaptosomes were incubated in calcium-replete medium. These data indicate that calcium plays an obligatory role in depolarization-elicited stimulation of synaptosomal oxidative processes.