SNAP-25 Modulation of Calcium Dynamics Underlies Differences in GABAergic and Glutamatergic Responsiveness to Depolarization

Claudia Verderio, Davide Pozzi, Elena Pravettoni, Francesca Inverardi, Ursula Schenk, Silvia Coco, Véronique Proux-Gillardeaux, Thierry Galli, Ornella Rossetto, Carolina Frassoni, Michela Matteoli

Research output: Contribution to journalArticle

Abstract

SNAP-25 is a component of the SNARE complex implicated in synaptic vesicle exocytosis. In this study, we demonstrate that hippocampal GABAergic synapses, both in culture and in brain, lack SNAP-25 and are resistant to the action of botulinum toxins type A and E, which cleave this SNARE protein. Relative to glutamatergic neurons, which express SNAP-25, GABAergic cells were characterized by a higher calcium responsiveness to depolarization. Exogenous expression of SNAP-25 in GABAergic interneurons lowered calcium responsiveness, and SNAP-25 silencing in glutamatergic neurons increased calcium elevations evoked by depolarization. Expression of SNAP-251-197 but not of SNAP-251-180 inhibited calcium responsiveness, pointing to the involvement of the 180-197 residues in the observed function. These data indicate that SNAP-25 is crucial for the regulation of intracellular calcium dynamics and, possibly, of network excitability. SNAP-25 is therefore a multifunctional protein that participates in exocytotic function both at the mechanistic and at the regulatory level.

Original languageEnglish
Pages (from-to)599-610
Number of pages12
JournalNeuron
Volume41
Issue number4
DOIs
Publication statusPublished - Feb 19 2004

ASJC Scopus subject areas

  • Neuroscience(all)

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