Inactivation kinetics of voltage-gated calcium channels in glutamatergic neurons are influenced by SNAP-25.

SNAP-25 forms part of the SNARE core complex that mediates membrane fusion. Biochemical and electrophysiological evidence supports an accessory role for SNAP-25 in interacting with voltage-gated calcium channels (VGCCs) to modulate channel activity. We recently reported that endogenous SNAP-25 negatively regulates VGCC activity in glutamatergic neurons from rat hippocampal cultures by shifting the voltage-dependence of inactivation of the predominant P/Q-type channel current in these cells. In the present study, we extend these findings by investigating the effect that manipulating endogenous SNAP-25 expression has on the inactivation kinetics of VGCC current in both glutamatergic and GABAergic cells recorded from 9-13 DIV cultures. Silencing SNAP-25 in glutamatergic neurons significantly slowed the inactivation rate of P/Q-type VGCC current whereas alterations in SNAP-25 expression did not alter inactivation rates in GABAergic neurons. These results indicate that endogenous SNAP-25 plays an important role in P/Q-type channel regulation in glutamatergic neurons.