title: Loss of auditory activity modifies the location of potassium channel KCNQ5 in auditory brainstem neurons.
abstract: KCNQ5/Kv7.5, a low-threshold noninactivating voltage-gated potassium channel, is preferentially targeted to excitatory endings of auditory neurons in the adult rat brainstem. Endbulds of Held from auditory nerve axons on the bushy cells of the ventral cochlear nucleus (VCN) and calyces of Held around the principal neurons in the medial nucleus of the trapezoid body (MNTB) are rich in KCNQ5 immunoreactivity. We have previously shown that this synaptic distribution occurs at about the time of hearing onset. The current study tests whether this localization in excitatory endings depends on the peripheral activity carried by the auditory nerve. Auditory nerve activity was abolished by cochlear removal or intracochlear injection of tetrodotoxin (TTX). Presence of KCNQ5 was analyzed by immunocytochemistry, Western blotting, and quantitative reverse transcription polymerase chain reaction. After cochlear removal, KCNQ5 immunoreactivity was virtually undetectable at its usual location in endbulbs and calyces of Held in the anteroventral CN and in the MNTB, respectively, although it was found in cell bodies in the VCN. The results were comparable after intracochlear TTX injection, which drastically reduced KCNQ5 immunostaining in MNTB calyces and increased immunolabeling in VCN cell bodies. Endbulbs of Held in the VCN also showed diminished KCNQ5 labeling after intracochlear TTX injection. These results show that peripheral activity from auditory nerve afferents is necessary to maintain the subcellular distribution of KCNQ5 in synaptic endings of the auditory brainstem. This may contribute to adaptations in the excitability and neurotransmitter release properties of these presynaptic endings under altered input conditions.
authors.affiliation: Instituto de Investigación en Discapacidades Neurológicas (IDINE), Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Caminos
authors.forename: Elisabet
authors.initials: E
authors.lastname: Garcia-Pino
authors.forename: Jose M
authors.initials: JM
authors.lastname: Juiz
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001304:Auditory Diseases, Central / Q000209:etiology* / Q000473:pathology*; D001933:Brain Stem / Q000473:pathology*; D064032:Calbindin 2 / Q000378:metabolism; D015834:Cochlear Diseases / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D064032:Calbindin 2; D005452:Fluoresceins; D051656:KCNQ Potassium Channels; C501028:Kcnq5 protein, rat; D012333:RNA, Messenger; C435731:fluoro jade; D013779:Tetrodotoxin
keywords: Kv7.5; TTX; auditory system; cochlear ablation; rat