Experimental diabetes enhances Ca2+ mobilization and glutamate exocytosis in cerebral synaptosomes from mice.

The present study was conducted to investigate the effects of the diabetic condition on the Ca(2+) mobilization and glutamate release in cerebral nerve terminals (synaptosomes). Diabetes was induced in male mice by intraperitoneal injection of streptozotocin. Cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and glutamate release in synaptosomes were determined using fura-2 and enzyme-linked fluorometric assay, respectively. Diabetes significantly enhanced the ability of the depolarizing agents K(+) and 4-aminopyridine (4-AP) to increase [Ca(2+)](i). In addition, diabetes significantly enhanced K(+)- and 4-AP-evoked Ca(2+)-dependent glutamate release. The pretreatment of synaptosomes with a combination of omega-agatoxin IVA (a P-type Ca(2+) channel blocker) and omega-conotoxin GVIA (an N-type Ca(2+) channel blocker) inhibited K(+)- or 4-AP-induced increases in [Ca(2+)](i) and Ca(2+)-dependent glutamate release in synaptosomes from the control and diabetic mice to a similar extent, respectively. These results indicate that diabetes enhances a K(+)- or 4-AP-evoked Ca(2+)-dependent glutamate release by increasing [Ca(2+)](i) via stimulation of Ca(2+) entry through both P- and N-type Ca(2+) channels.