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

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 and on presynaptic calcium currents 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 approximately 30%. A clinical highconcentration dose of PGB (e.g., 500 _M) blocked Cav2.1 channel- mediated currents and decreased their facilitation during a 100-Hz train, without changing their voltage-dependent activation. Furthermore, PGB also removed the inactivation of Cav2.1 channels at a clinically relevant low concentration of 100 _M. 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.