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

Carlotta Grumelli, Irene Corradini, Michela Matteoli, Claudia Verderio

Research output: Contribution to journalArticle

Abstract

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-251-197 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.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
JournalCell Calcium
Volume47
Issue number5
DOIs
Publication statusPublished - May 2010

Fingerprint

Type A Botulinum Toxins
Calcium
Population
Exocytosis
Synapses
Neurons
SNARE Proteins
Calcium Channels

Keywords

  • Botulinum A
  • Calcium transients
  • Exocytosis
  • GABAergic neurons
  • Glutamatergic neurons
  • SNAP-25

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations. / Grumelli, Carlotta; Corradini, Irene; Matteoli, Michela; Verderio, Claudia.

In: Cell Calcium, Vol. 47, No. 5, 05.2010, p. 419-424.

Research output: Contribution to journalArticle

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