Modulation of calcium-dependent and -independent components of veratridine-evoked release of glutamate from rat cerebellum.
The entry of Ca2+ into the presynaptic neuronal terminal is considered to be a prerequisite for exocytosis. However, reports suggest that a Ca(2+)-independent component of release can exist for some neurotransmitters. In this study we have used veratridine-stimulated release of glutamate from rat cerebellar slices to investigate Ca(2+)-dependent and -independent release. A 1-min pulse of veratridine (10 microM) induced release of glutamate in both Ca(2+)-replete and Ca(2+)-free ACSF. Both modes of release, however, could be elicited in a sequential manner following a single application of veratridine in Ca(2+)-free ACSF, with return to Ca(2+)-replete conditions 5 min post-pulse. This separation permitted the modulation of either, or both, phases of release. Apamin and dihydrokainate had little effect on Ca(2+)-independent release but produced enhancement of the Ca(2+)-dependent phase. Tetrodotoxin abolished both phases of release when applied with the veratridine pulse, but had no effect on the Ca(2+)-dependent phase alone. The Ca(2+)-dependent phase was partially sensitive to Co2+, although the Ca2+ channel blockers verapamil, amiloride, omega-conotoxin and ruthenium red were ineffective, suggesting a lack of involvement of L-, N- or T-type channels. The possible mechanisms mediating the Ca(2+)-dependent and -independent components of endogenous glutamate release from cerebellar slices are discussed.
Dickie
B G
BG
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, UK.
Davies
J A
JA
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D010455:Peptides / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D005971:Glutamates; D010455:Peptides; D020960:omega-Conotoxins; C053423:Conus magus toxin; D012430:Ruthenium Red; D001030:Apamin; D001224:Aspartic Acid; D003035:Cobalt; D018698:Glutamic Acid; D013779:Tetrodotoxin; C020889:dihydrokainic acid; D014701:Veratridine; D000584:Amiloride; D014700:Verapamil; D007608:Kainic Acid; D002118:Calcium