Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations

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• 作者：Carlotta Grumelli ; Irene Corradini ; Michela Matteoli ; Claudia Verderio
• 关键词：Botulinum A ; GABAergic neurons ; SNAP-25 ; Glutamatergic neurons ; Calcium transients ; Exocytosis
• 刊名：Cell Calcium
• 出版年：2010
• 出版时间：May 2010
• 年：2010
• 卷：47
• 期：5
• 页码：419-424
• 全文大小：2272 K

文摘

SNAP-25 is a SNARE protein implicated in exocytosis and in the negative modulation of voltage-gated calcium channels. We have previously shown that GABAergic synapses, which express SNAP-25 at much lower levels relative to glutamatergic ones, are characterized by a higher calcium responsiveness to depolarization and are largely resistant to botulinum toxin A. We show here that silencing of SNAP-25 in glutamatergic neurons, a procedure which increases KCl-induced calcium elevations, confers these synapses with toxin resistance. Since it is known that calcium reverts the efficacy of botulinum A, we investigated whether the lower effectiveness of the toxin in inhibiting GABAergic vesicle cycling might be attributable to higher evoked calcium transients of inhibitory neurons. We demonstrate that either expression of SNAP-25_1–197 or BAPTA/AM treatment, both inhibiting calcium dynamics, facilitate block of GABAergic vesicle exocytosis upon toxin treatment. These data indicate that intrinsic calcium dynamics control botulinum A susceptibility in distinct neuronal populations.