Endogenous SNAP-25 regulates native voltage-gated calcium channels in glutamatergic neurons. (Articolo in rivista)

Type
Label
  • Endogenous SNAP-25 regulates native voltage-gated calcium channels in glutamatergic neurons. (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Condliffe SB, Corradini I, Pozzi D, Verderio C and Matteoli M (2010)
    Endogenous SNAP-25 regulates native voltage-gated calcium channels in glutamatergic neurons.
    in The Journal of biological chemistry (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Condliffe SB, Corradini I, Pozzi D, Verderio C and Matteoli M (literal)
Pagina inizio
  • 24968 (literal)
Pagina fine
  • 24976 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 285 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Univ Milan, Dept Med Pharmacol, I-20129 Milan, Italy 2. Univ Milan, CNR, Inst Neurosci, I-20129 Milan, Italy 3. IRCCS Fdn Don Gnocchi, I-20122 Milan, Italy (literal)
Titolo
  • Endogenous SNAP-25 regulates native voltage-gated calcium channels in glutamatergic neurons. (literal)
Abstract
  • 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. (literal)
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