In addition to its primary role as a fundamental component of the SNARE complex, SNAP-25 also modulates voltage-gated calcium channels (VGCCs) in various overexpression systems. Although these studies suggest a potential negative regulatory role of SNAP-25 on VGCC activity, the effects of endogenous SNAP-25 on native VGCC function in neurons are unclear. In the present study, we investigated the VGCC properties of cultured glutamatergic and GABAergic rat hippocampal neurons. Glutamatergic currents were dominated by P/Q-type channels, whereas GABAergic cells had a dominant L-type component. Also, glutamatergic VGCC current densities were significantly lower with enhanced inactivation rates and shifts in the voltage dependence of activation and inactivation curves compared with GABAergic cells. Silencing endogenous SNAP-25 in glutamatergic neurons did not alter P/Q-type channel expression or localization but led to increased VGCC current density without changes in the VGCC subtype proportions. Isolation of the P/Qtype component indicated that increased current in the absence of SNAP-25 was correlated with a large depolarizing shift in the voltage dependence of inactivation. Overexpressing SNAP-25 in GABAergic neurons reduced current density without affecting the VGCC subtype proportion. Accordingly, VGCC current densities in glutamatergic neurons from Snap-25(+/-) mice were significantly elevated compared with wild type glutamatergic neurons. Overall, this study demonstrates that endogenous SNAP-25 negatively regulates native VGCCs in glutamatergic neurons which could have important implications for neurological diseases associated with altered SNAP-25 expression.
Endogenous SNAP-25 Regulates Native Voltage-gated Calcium Channels in Glutamatergic Neurons / S.B. Condliffe, I. Corradini, D. Pozzi, C. Verderio, M. Matteoli. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 285:32(2010 Aug), pp. 24968-24976.
|Titolo:||Endogenous SNAP-25 Regulates Native Voltage-gated Calcium Channels in Glutamatergic Neurons|
CONDLIFFE, STEVEN BRUCE (Primo)
CORRADINI, IRENE (Secondo)
MATTEOLI, MICHELA (Ultimo)
|Parole Chiave:||Ca2+ Channels ; Hippocampal-Neurons ; Subcellular-Distribution ; Alpha(1a) Subunits ; Protein Snap-25 ; Mouse ; Schizophrenia ; Expression ; Syntaxin ; Snare|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Progetto:||European consortium on synaptic protein networks in Neurological and Psychiatric diseases|
|Data di pubblicazione:||ago-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M110.145813|
|Appare nelle tipologie:||01 - Articolo su periodico|