Pregabalin modulation of calcium channels and neurotransmitter release

DI GUILMI MN ; URBANO FJ; GONZALEZ-INCHAUSPE C; UCHITEL OD

Huerta Grande, Cordoba, Argentina

Congreso; IIRCN- Second Joint Meeting of the Argentine Society for Neuroscience (SAN: XXV Reunion Anual de la Sociedad Argentina de Investigacion en Neurociencias) and the Argentine Workshop in Neuroscience (TAN: XII Taller Argentino de Neurociencias).; 2010

SAN-TAN

In this work we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse Medial Nucleus of the Trapezoid Body (MNTB), as well as on presynaptic calcium currents (IpCa) at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect of about 30%. A clinical high-concentration dose of PGB (e.g., 500 microM) blocked CaV2.1 channel-mediated currents and decreased their facilitation during 100 Hz train, without changing their voltage-dependent activation. Furthermore, PGB also favored the recovery of CaV2.1 channels after inactivation at a clinically relevant low concentration of 100 microM. These results suggest novel modulatory mechanisms mediated by the acute administration of PGB on fast excitatory synaptic transmission and might contribute to better understanding PGB anticonvulsant/analgesic clinical effects.