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.
Satoh
Eiki
E
Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan. es@obihiro.ac.jp
Takahashi
Ayako
A
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020867:omega-Agatoxin IVA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020867:omega-Agatoxin IVA; D018698:Glutamic Acid; D011188:Potassium; D002118:Calcium