info:eu-repo/semantics/article
Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
Fecha
2011-03Registro en:
Di Guilmi, Mariano Nicolás; Urbano Suarez, Francisco Jose; González Inchauspe, Carlota María Fabiola; Uchitel, Osvaldo Daniel; Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels; American Society for Pharmacology and Experimental Therapeutics; Journal of Pharmacology and Experimental Therapeutics; 336; 3; 3-2011; 973-982
0022-3565
CONICET Digital
CONICET
Autor
Di Guilmi, Mariano Nicolás
Urbano Suarez, Francisco Jose
González Inchauspe, Carlota María Fabiola
Uchitel, Osvaldo Daniel
Resumen
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 high-concentration dose of PGB (e.g., 500 μM) 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 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.