A novel Ca V 2.2 channel inhibition by piracetam in peripheral and central neurons

Abstract

No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca_V2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca_V2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca_V2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC₅₀ of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca_V2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca_V2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca_V2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.