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Abstract:

Striatal cholinergic interneurons provide modulation to striatal circuits involved in voluntary motor control and goal-directed behaviors through their autonomous tonic discharge and their firing “pause” responses to novel and rewarding environmental events. Striatal cholinergic interneuron hyperactivity was linked to the motor deficits associated with Parkinson's disease and the adverse effects of chronic antiparkinsonian therapy like L-DOPA-induced dyskinesia. Here we addressed whether Kv7 channels, which provide negative feedback to excitation in other neuron types, are involved in the control of striatal cholinergic interneuron tonic activity and response to excitatory inputs. We found that autonomous firing of striatal cholinergic interneurons is not regulated by Kv7 channels. In contrast, Kv7 channels limit the summation of excitatory postsynaptic potentials in cholinergic interneurons through a postsynaptic mechanism. Striatal cholinergic interneurons have a high reserve of Kv7 channels, as their opening using pharmacological tools completely silenced the tonic firing and markedly reduced their intrinsic excitability. A strong inhibition of striatal cholinergic interneurons was also observed in response to the anti-inflammatory drugs diclofenac and meclofenamic acid, however, this effect was independent of Kv7 channels. These data bring attention to new potential molecular targets and pharmacological tools to control striatal cholinergic interneuron activity in pathological conditions where they are believed to be hyperactive, including Parkinson's disease. © 2018 Elsevier Ltd

Registro:

Documento: Artículo
Título:Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac
Autor:Paz, R.M.; Tubert, C.; Stahl, A.; Díaz, A.L.; Etchenique, R.; Murer, M.G.; Rela, L.
Filiación:Universidad de Buenos Aires y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Fisiología y Biofísica “Bernardo Houssay” (IFIBIO-Houssay), Grupo de Neurociencia de Sistemas, Buenos Aires, 1121, Argentina
Departamento de Química Inorgánica, Analítica y Química Física, INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Ciudad Universitaria Pabellón 2, AR1428EHA Buenos Aires, Argentina
Robert H. Lurie Medical Research Center of Northwestern University, Department of Physiology, 303 East Superior Street, Chicago, IL 60611, United States
Palabras clave:Diclofenac; Excitability; Kv7; Retigabine; Striatal cholinergic interneurons; Synaptic integration; diclofenac; meclofenamic acid; potassium channel; potassium channel Kv7; retigabine; unclassified drug; acetylcholine; agents affecting water, molecule or ion transport; carbamic acid derivative; diclofenac; nonsteroid antiinflammatory agent; phenylenediamine derivative; potassium channel; potassium channel blocking agent; retigabine; animal tissue; Article; excitatory postsynaptic potential summation; interneuron; male; mouse; negative feedback; nerve cell excitability; nerve cell inhibition; nerve cell stimulation; neuromodulation; neurotransmission; nonhuman; priority journal; striatal cholinergic interneuron; animal; corpus striatum; drug effect; excitatory postsynaptic potential; interneuron; metabolism; physiology; tissue culture technique; transgenic mouse; Acetylcholine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbamates; Corpus Striatum; Diclofenac; Excitatory Postsynaptic Potentials; Interneurons; Male; Membrane Transport Modulators; Mice, Transgenic; Phenylenediamines; Potassium Channel Blockers; Potassium Channels; Tissue Culture Techniques
Año:2018
Volumen:137
Página de inicio:309
Página de fin:321
DOI: http://dx.doi.org/10.1016/j.neuropharm.2018.05.010
Título revista:Neuropharmacology
Título revista abreviado:Neuropharmacology
ISSN:00283908
CODEN:NEPHB
CAS:diclofenac, 15307-79-6, 15307-86-5; meclofenamic acid, 644-62-2; retigabine, 150812-12-7, 150812-13-8; acetylcholine, 51-84-3, 60-31-1, 66-23-9; Acetylcholine; Anti-Inflammatory Agents, Non-Steroidal; Carbamates; Diclofenac; ezogabine; Membrane Transport Modulators; Phenylenediamines; Potassium Channel Blockers; Potassium Channels
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v137_n_p309_Paz

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Citas:

---------- APA ----------
Paz, R.M., Tubert, C., Stahl, A., Díaz, A.L., Etchenique, R., Murer, M.G. & Rela, L. (2018) . Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac. Neuropharmacology, 137, 309-321.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.010
---------- CHICAGO ----------
Paz, R.M., Tubert, C., Stahl, A., Díaz, A.L., Etchenique, R., Murer, M.G., et al. "Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac" . Neuropharmacology 137 (2018) : 309-321.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.010
---------- MLA ----------
Paz, R.M., Tubert, C., Stahl, A., Díaz, A.L., Etchenique, R., Murer, M.G., et al. "Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac" . Neuropharmacology, vol. 137, 2018, pp. 309-321.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.010
---------- VANCOUVER ----------
Paz, R.M., Tubert, C., Stahl, A., Díaz, A.L., Etchenique, R., Murer, M.G., et al. Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac. Neuropharmacology. 2018;137:309-321.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.010