Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac
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 hyperact...
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todo:paper_00283908_v137_n_p309_Paz2023-10-03T14:39:01Z Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac Paz, R.M. Tubert, C. Stahl, A. Díaz, A.L. Etchenique, R. Murer, M.G. Rela, L. 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 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 JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00283908_v137_n_p309_Paz |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Paz, R.M. Tubert, C. Stahl, A. Díaz, A.L. Etchenique, R. Murer, M.G. Rela, L. Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac |
| topic_facet |
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 |
| description |
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 |
| format |
JOUR |
| author |
Paz, R.M. Tubert, C. Stahl, A. Díaz, A.L. Etchenique, R. Murer, M.G. Rela, L. |
| author_facet |
Paz, R.M. Tubert, C. Stahl, A. Díaz, A.L. Etchenique, R. Murer, M.G. Rela, L. |
| author_sort |
Paz, R.M. |
| title |
Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac |
| title_short |
Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac |
| title_full |
Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac |
| title_fullStr |
Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac |
| title_full_unstemmed |
Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac |
| title_sort |
inhibition of striatal cholinergic interneuron activity by the kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac |
| url |
http://hdl.handle.net/20.500.12110/paper_00283908_v137_n_p309_Paz |
| work_keys_str_mv |
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| _version_ |
1807315448861032448 |