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A Late Phase of Exocytosis from Synaptosomes Induced by Elevated [Ca 2+ ] i Is Not Blocked by Clostridial Neurotoxins
Author(s) -
Ashton Anthony C.,
Dolly J. Oliver
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741979.x
Subject(s) - exocytosis , synaptobrevin , glutamate receptor , ionophore , neurotoxin , synaptic vesicle , chemistry , biochemistry , syntaxin , calcium , neurotransmitter , depolarization , biophysics , biology , secretion , receptor , vesicle , membrane , organic chemistry
Treatment of rat cerebrocortical synaptosomes with botulinum toxin types E and C1 or tetanus toxin removed the majority of intact SNAP‐25, syntaxin 1A/1B, and synaptobrevin and diminished Ca 2+ ‐dependent K + depolarization‐induced noradrenaline secretion. With botulinum toxin type E, <10% of intact SNAP‐25 remained and K + ‐evoked release of glutamate and GABA was inhibited. The large component of noradrenaline release evoked within 120 s by inclusion of the Ca 2+ ionophore A23187 with the K + stimulus was also attenuated by these toxins; additionally, botulinium neurotoxin type E blocked the first 60 s of ionophore‐induced GABA and glutamate exocytosis. However, exposure to A23187 for longer periods induced a phase of secretion nonsusceptible to any of these toxins (>120 s for noradrenaline; >60 s for glutamate or GABA). Most of this late phase of release represented exocytosis because of its Ca 2+ dependency, ATP requirement, and sensitivity to a phosphatidylinositol 4‐kinase inhibitor. Based on these collective findings, we suggest that the ionophore‐induced elevation of [Ca 2+ ] i culminates in the disassembly of complexes containing nonproteolyzed SNAP receptors protected from the toxins that can then contribute to neuroexocytosis.