title: A novel CaV2.2 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(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 IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS 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 ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.
authors.affiliation: Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México, México, D.F., México.
authors.forename: Jorge
authors.initials: J
authors.lastname: Bravo-Martínez
authors.forename: Isabel
authors.initials: I
authors.lastname: Arenas
authors.forename: Oscar
authors.initials: O
authors.lastname: Vivas
authors.forename: Santiago
authors.initials: S
authors.lastname: Rebolledo-Antúnez
authors.forename: Mario
authors.initials: M
authors.lastname: Vázquez-García
authors.forename: Arturo
authors.initials: A
authors.lastname: Larrazolo
authors.forename: David E
authors.initials: DE
authors.lastname: García
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010889:Piracetam / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000166:cytology* / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018697:Nootropic Agents; D043562:Receptors, G-Protein-Coupled; D010889:Piracetam