Acute modulation of calcium currents and synaptic transmission by gabapentinoids
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 t...
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todo:paper_19336950_v4_n6_p_Uchitel2023-10-03T16:36:12Z Acute modulation of calcium currents and synaptic transmission by gabapentinoids Uchitel, O.D. Di Guilmi, M.N. Urbano, F.J. Inchauspe, C.G. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19336950_v4_n6_p_Uchitel |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Uchitel, O.D. Di Guilmi, M.N. Urbano, F.J. Inchauspe, C.G. Acute modulation of calcium currents and synaptic transmission by gabapentinoids |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Uchitel, O.D. Di Guilmi, M.N. Urbano, F.J. Inchauspe, C.G. |
| author_facet |
Uchitel, O.D. Di Guilmi, M.N. Urbano, F.J. Inchauspe, C.G. |
| author_sort |
Uchitel, O.D. |
| title |
Acute modulation of calcium currents and synaptic transmission by gabapentinoids |
| title_short |
Acute modulation of calcium currents and synaptic transmission by gabapentinoids |
| title_full |
Acute modulation of calcium currents and synaptic transmission by gabapentinoids |
| title_fullStr |
Acute modulation of calcium currents and synaptic transmission by gabapentinoids |
| title_full_unstemmed |
Acute modulation of calcium currents and synaptic transmission by gabapentinoids |
| title_sort |
acute modulation of calcium currents and synaptic transmission by gabapentinoids |
| url |
http://hdl.handle.net/20.500.12110/paper_19336950_v4_n6_p_Uchitel |
| work_keys_str_mv |
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1807322006384803840 |