Experimental diabetes enhances Ca 2+ mobilization and glutamate exocytosis in cerebral synaptosomes from mice

Abstract

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 ω-agatoxin IVA (a P-type Ca 2+ channel blocker) and ω-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.