Time course and role of extracellular Ca2+ in veratridine-induced glutamate release

The veratridine-induced release of glutamate in the striatum of anaesthetized rats was studied using regional brain microdialysis to elucidate the role of extracellular Ca2+ and to investigate the exact time course of the glutamate response. In a first series of experiments with Ca(2+)-depletion starting simultaneously with the veratridine pulse no significant differences were found under Ca(2+)-replete and Ca(2+)-free conditions. Strikingly, under both conditions glutamate efflux followed a biphasic time course. When Ca2+ depletion preceded veratridine stimulation a significant inhibition of the initial glutamate release was found, indicating that the first glutamate portion originates from Ca(2+)-dependent vesicular exocytosis. The nature of the second and longer lasting phase of glutamate efflux is not clear, but it may be mediated by reversal of the glutamate uptake system of the plasma membrane located both on neurones and on astrocytes. This points to a possibly important contribution of glial cells to glutamate overflow under pathological conditions and should be subject to further investigations.