Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of CaV2.1 calcium channels

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

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS

Año: 2011 vol. 336 p. 973 - 982

0022-3565

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 remove the inactivation of CaV2.1 channels at a clinically relevant low concentration of 100 μM. 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.