Pregabalin modulation of calcium channels and neurotransmitter release

DI GUILMI MARIANO N.; URBANO FRANCISCO J.; GONZáLEZ INCHAUSPE C.; UCHITEL O.D.

Huerta Grande, Córdoba, Argentina

Congreso; II Reunión Conjunta de la Sociedad Argentina de Neurociencias; 2010

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 ìM) 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 ìM. 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.