Measurements of exocytosis from single presynaptic nerve terminals reveal heterogeneous inhibition by Ca(2+)-channel blockers.
The effect of various Ca(2+)-channel blockers on exocytosis has been studied at the level of single presynaptic terminals in rat hippocampal cell cultures. The fluorescence change of the styryl dye FM 1-43 has been used as a measure of exocytosis during electrical stimulation. omega-Conotoxin GVIA (2-10 microM) completely inhibited exocytosis in approximately 45% of the boutons in the field of view, while in approximately 55% exocytosis was inhibited incompletely (by 38%). This heterogeneity in response of presynaptic boutons was not seen with isradipine (5 microM) or omega-agatoxin IVA (80 nM), which inhibited exocytosis by 23% and 17%, respectively. However, it was observed with a combination of all three blockers. Pre- and postsynaptic events could be separated in single synapses by measuring FM1-43 release and NMDA-induced changes in the intracellular Ca2+ concentration independently.
Reuter
H
H
Department of Pharmacology, University of Bern, Switzerland.
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects*; D006624:Hippocampus / Q000648:ultrastructure*; D017275:Isradipine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology; D013569:Synapses / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; C073804:FM1 43; D010455:Peptides; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D011189:Potassium Chloride; D020866:omega-Conotoxin GVIA; D002118:Calcium; D017275:Isradipine