Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing

Autor: Taranda, J., Ballestero, J.A., Hiel, H., De Souza, F.S.J., Wedemeyer, C., Gómez-Casati, M.E., Lipovsek, M., Vetter, D.E., Fuchs, P.A., Katz, E., Elgoyhen, A.B.
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Patch-Clamp Techniques
Small-Conductance Calcium-Activated Potassium Channels
Cholinergic Agents
complementary DNA
Kcnn2 protein
mouse
Receptors
Nicotinic
cholinergic receptor stimulating agent
potassium channel SK2
Mice
Hearing
Transgenic mice
animal
genetics
Pou4f3 protein
mouse
Pou4f3 gene
messenger RNA
drug effect
article
unclassified drug
Transcription Factor Brn-3C
receptor gene
priority journal
small conductance calcium activated potassium channel
Models
Animal
wild type
SK2 channel
down regulation
transcription factor POU4F3
animal experiment
Mice
Transgenic
hair cell
patch clamp
animal tissue
promoter region
potassium current
Animals
controlled study
RNA
Messenger
cholinergic synapse
mouse
Homeodomain Proteins
nonhuman
Hair Cells
Auditory
Inner
RNA translation
nicotinic acetylcholine receptor alpha10
animal model
efferent nerve
transgene
genetic transcription
Chrna10 gene
acetylcholine
Nicotinic cholinergic receptors
Chrna10 protein
mouse
transgenic mouse
homeodomain protein
physiology
evoked response
gene expression
cytology
in situ hybridization
receptor subunit
nicotinic receptor
metabolism
Efferent medial olivocochlear
Zdroj: JARO J. Assoc. Res. Otolaryngol. 2009;10(3):397-406
Biblioteca Digital (UBA-FCEN)
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron:UBA-FCEN
Popis: Efferent inhibition of cochlear hair cells is mediated by α9α10 nicotinic cholinergic receptors (nAChRs) functionally coupled to calcium-activated, small conductance (SK2) potassium channels. Before the onset of hearing, efferent fibers transiently make functional cholinergic synapses with inner hair cells (IHCs). The retraction of these fibers after the onset of hearing correlates with the cessation of transcription of the Chrna10 (but not the Chrna9) gene in IHCs. To further analyze this developmental change, we generated a transgenic mice whose IHCs constitutively express α10 into adulthood by expressing the α10 cDNA under the control of the Pou4f3 gene promoter. In situ hybridization showed that the α10 mRNA is expressed in IHCs of 8-week-old transgenic mice, but not in wild-type mice. Moreover, this mRNA is translated into a functional protein, since IHCs from P8-P10 α10 transgenic mice backcrossed to a Chrna10 -/- background (whose IHCs have no cholinergic function) displayed normal synaptic and acetylcholine (ACh)-evoked currents in patch-clamp recordings. Thus, the α10 transgene restored nAChR function. However, in the α10 transgenic mice, no synaptic or ACh-evoked currents were observed in P16-18 IHCs, indicating developmental down-regulation of functional nAChRs after the onset of hearing, as normally observed in wild-type mice. The lack of functional ACh currents correlated with the lack of SK2 currents. These results indicate that multiple features of the efferent postsynaptic complex to IHCs, in addition to the nAChR subunits, are down-regulated in synchrony after the onset of hearing, leading to lack of responses to ACh. © 2009 Association for Research in Otolaryngology. Fil:Taranda, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ballestero, J.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wedemeyer, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gómez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lipovsek, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Databáze: OpenAIRE
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