Rapid chelation of calcium entering isolated rat brain nerve terminals during stimulation inhibits neurotransmitter release.
The intracellular actions of calcium chelators on the release of the neurotransmitter glutamate from isolated rat brain nerve terminals (synaptosomes) were examined. Preloading synaptosomes with the rapid calcium-binding chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) resulted in a decrease in K(+)-stimulated glutamate release to nearly half that of controls, whereas preloading with the calcium chelator EGTA, whose action is less rapid than that of BAPTA, was without effect. Inhibition of glutamate release was also observed on preloading synaptosomes with dibromo-BAPTA, but not with dinitro-BAPTA. K(+)-stimulated, Ca2(+)-dependent synaptosomal protein phosphorylation was not affected after preloading with BAPTA. The results suggest that the calcium-dependent intracellular component essential for triggering the secretory response in mammalian brain nerve terminals resides near the calcium channels, binding calcium rapidly on its entry during stimulation.
Nichols
R A
RA
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, USA. nichols@medcolpa.edu
Suplick
G R
GR
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D002614:Chelating Agents; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium