title: Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of ca(v)2.1 calcium channels.
abstract: 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 Ca(v)2.1 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 Ca(v)2.1 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.
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: Mariano N
authors.initials: MN
authors.lastname: Di Guilmi
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Urbano
authors.forename: Carlota Gonzalez
authors.initials: CG
authors.lastname: Inchauspe
authors.forename: Osvaldo D
authors.initials: OD
authors.lastname: Uchitel
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism*; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D020864:Calcium Channels, N-Type; D018377:Neurotransmitter Agents; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid