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.
Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations / C. Grumelli, I. Corradini, M. Matteoli, C. Verderio. - In: CELL CALCIUM. - ISSN 0143-4160. - 47:5(2010), pp. 419-424.
|Titolo:||Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations|
GRUMELLI, CARLOTTA (Primo)
CORRADINI, IRENE (Secondo)
MATTEOLI, MICHELA (Penultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Progetto:||European consortium on synaptic protein networks in Neurological and Psychiatric diseases|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ceca.2010.03.002|
|Appare nelle tipologie:||01 - Articolo su periodico|