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Abstract:

Gabapentin and pregabalin are anticonvulsant drugs that are extensively used for the treatment of several neurological and psychiatric disorders. Gabapentinoids (GBPs) are known to have a high affinity binding to α2δ-1 and α2δ-2 auxiliary subunit of specific voltage-gated calcium channels. Despite the confusing effects reported on Ca2+ currents, most of the studies showed that GBPs reduced release of various neurotransmitters from synapses in several neuronal tissues. We showed that acute in vitro application of pregabalin could reduce in a dose dependent manner synaptic transmission in both neuromuscular junctions and calyx of Held-MNTB excitatory synapses. Furthermore presynaptic Ca 2+ currents treated with pregabalin are reduced in amplitude, do not show inactivation at a clinically relevant low concentration of 100 μM and activate and deactive faster. These results suggest novel modulatory role of acute pregabalin that might contribute to better understanding its anticonvulsant/analgesic clinical effects. © 2010 Landes Bioscience.

Registro:

Documento: Artículo
Título:Acute modulation of calcium currents and synaptic transmission by gabapentinoids
Autor:Uchitel, O.D.; Di Guilmi, M.N.; Urbano, F.J.; Inchauspe, C.G.
Filiación:Instituto de Fisiología; Biología Molecular Y Neurociencias (IFIBYNE), Departamento de Fisiología, Biología Molecular Y Celular, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Calcium channels; Calyx of held; Gabapentin; Mice; Neuromuscular junction; Pregabalin; Synaptic transmission; 4 aminobutyric acid; amino acid transporter; calcium channel P type; calcium channel Q type; gabapentin; glycine; n methyl dextro aspartic acid; neurotransmitter; potassium channel; pregabalin; sodium channel; thrombospondin; voltage gated calcium channel; 4 aminobutyric acid; amine; anticonvulsive agent; calcium channel; cyclohexanecarboxylic acid derivative; drug derivative; gabapentin; ligand; pregabalin; binding affinity; calcium current; central nervous system; dose response; drug protein binding; drug targeting; electrophysiology; human; ligand binding; modulation; neurochemistry; neuromuscular synapse; neurotransmitter release; nonhuman; protein interaction; review; skeletal muscle; spinal ganglion; synaptic transmission; animal; binding competition; binding site; brain; calcium signaling; drug effect; kinetics; metabolism; synapse; synaptic potential; synaptosome; Mus; Amines; Animals; Anticonvulsants; Binding Sites; Binding, Competitive; Brain; Calcium Channels; Calcium Signaling; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Humans; Kinetics; Ligands; Presynaptic Terminals; Synapses; Synaptic Potentials; Synaptic Transmission
Año:2010
Volumen:4
Número:6
DOI: http://dx.doi.org/10.4161/chan.4.6.12864
Título revista:Channels
Título revista abreviado:Channels
ISSN:19336950
CAS:4 aminobutyric acid, 28805-76-7, 56-12-2; gabapentin, 60142-96-3; glycine, 56-40-6, 6000-43-7, 6000-44-8; n methyl dextro aspartic acid, 6384-92-5; pregabalin, 148553-50-8; Amines; Anticonvulsants; Calcium Channels; Cyclohexanecarboxylic Acids; gabapentin, 60142-96-3; gamma-Aminobutyric Acid, 56-12-2; Ligands; pregabalin
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19336950_v4_n6_p_Uchitel

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Citas:

---------- APA ----------
Uchitel, O.D., Di Guilmi, M.N., Urbano, F.J. & Inchauspe, C.G. (2010) . Acute modulation of calcium currents and synaptic transmission by gabapentinoids. Channels, 4(6).
http://dx.doi.org/10.4161/chan.4.6.12864
---------- CHICAGO ----------
Uchitel, O.D., Di Guilmi, M.N., Urbano, F.J., Inchauspe, C.G. "Acute modulation of calcium currents and synaptic transmission by gabapentinoids" . Channels 4, no. 6 (2010).
http://dx.doi.org/10.4161/chan.4.6.12864
---------- MLA ----------
Uchitel, O.D., Di Guilmi, M.N., Urbano, F.J., Inchauspe, C.G. "Acute modulation of calcium currents and synaptic transmission by gabapentinoids" . Channels, vol. 4, no. 6, 2010.
http://dx.doi.org/10.4161/chan.4.6.12864
---------- VANCOUVER ----------
Uchitel, O.D., Di Guilmi, M.N., Urbano, F.J., Inchauspe, C.G. Acute modulation of calcium currents and synaptic transmission by gabapentinoids. Channels. 2010;4(6).
http://dx.doi.org/10.4161/chan.4.6.12864