title: The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo.
abstract: Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener retigabine. The effect of retigabine likely involves the inhibition of the activity in mesencephalic dopaminergic neurons projecting to the striatum, but whether Kv7 channels expressed in the striatum may also play a role is not resolved. We therefore assessed the effect of intrastriatal retigabine administration on striatal neuronal excitability in the rat determined by c-Fos immunoreactivity, a marker of neuronal activation. When retigabine was applied locally in the striatum, this resulted in a marked reduction in the number of c-Fos-positive neurons after a strong excitatory striatal stimulus induced by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo.
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Denmark.|NeuroSearch A/S, Ballerup, Denmark.
authors.forename: Henrik H
authors.initials: HH
authors.lastname: Hansen
authors.affiliation: Neuropsychiatric Laboratory, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Weikop
authors.affiliation: NeuroSearch A/S, Ballerup, Denmark.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Mikkelsen
authors.affiliation: NeuroSearch A/S, Ballerup, Denmark.
authors.forename: Frederik
authors.initials: F
authors.lastname: Rode
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Denmark.|NeuroSearch A/S, Ballerup, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Mikkelsen
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000071080:Cortical Excitability / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D007276:Injections, Intraventricular; D051656:KCNQ Potassium Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D008297:Male; D049990:Membrane Transport Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009476:Neurons, Efferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects; D010655:Phenylenediamines / Q000008:administration & dosage / Q000494:pharmacology*; D021122:Protein Subunits / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D015415:Biomarkers; D002219:Carbamates; D018492:Dopamine Antagonists; D051656:KCNQ Potassium Channels; D049990:Membrane Transport Modulators; D009419:Nerve Tissue Proteins; D010655:Phenylenediamines; D021122:Protein Subunits; D016760:Proto-Oncogene Proteins c-fos; C101866:ezogabine; D006220:Haloperidol