A novel Ca(v)2.2 channel inhibition by piracetam in peripheral and central neurons

作者：Bravo Martinez Jorge; Arenas Isabel; Vivas Oscar; Rebolledo Antunez Santiago; Vazquez Garcia Mario; Larrazolo Arturo; Garcia David E^*

来源：Experimental Biology and Medicine, 2012, 237(10): 1209-1218.

DOI：10.1258/ebm.2012.012128

• piracetam
• Ca(v)2.2 channels
• G-proteins
• SCG neurons
• CA1 hippocampal neurons
• hyperexcitability

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(v)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(v)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(v)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC50 of 3.4 mu mol/L and a Hill coefficient of 1.1. GDP/3S dialysis did not prevent piracetam-induced inhibition of Ca(v)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(v)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and omega-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam%26apos;s actions on Ca(v)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

• 出版日期2012-10