Calcium-dependent glutamate release concomitant with massive potassium flux during cerebral ischemia in vivo.

The changes in extracellular glutamate ([Glu]e) and potassium ([K+]e) in the rat hippocampus during cerebral ischemia were determined simultaneously by microdialysis in vivo. Biphasic increases in [Glu]e, i.e. an earlier rapid increase concomitant with an abrupt increase in [K+]e followed by a later slow increase, were observed. Dialysis with Ca(2+)-free perfusate containing Co2+ blocked the earlier rapid increase completely but the later slow increase only partially. These findings suggest that Ca(2+)-dependent exocytotic release from the presynaptic nerve terminals is involved predominantly in the earlier rapid increase in [Glu]d. The later slow increase in [Glu]d may be due in part to a breakdown of membrane function resulting from several causes, including a loss of the electrogenic component of the glutamate gradients across the plasma membrane, and a loss of function of the glutamate uptake system.