Developmental regulation of nicotinic synapses on cochlear inner hair cells

Authors
<div class="autor_fcen" id="4549">Katz, E.</div>; Elgoyhen, A.B.; <div class="autor_fcen" id="3830">Gómez-Casati, M.E.</div>; Knipper, M.; Vetter, D.E.; Fuchs, P.A.; Glowatzki, E.
Publication Year
2004
Language
English
Format
article
Status
Published version
Description
In the mature cochlea, inner hair cells (IHCs) transduce acoustic signals into receptor potentials, communicating to the brain by synaptic contacts with afferent fibers. Before the onset of hearing, a transient efferent innervation is found on IHCs, mediated by a nicotinic cholinergic receptor that may contain both α9 and α10 subunits. Calcium influx through that receptor activates calcium-dependent (SK2-containing) potassium channels. This inhibitory synapse is thought to disappear after the onset of hearing [after postnatal day 12 (P12)]. We documented this developmental transition using whole-cell recordings from IHCs in apical turns of the rat organ of Corti. Acetylcholine elicited ionic currents in 88-100% of IHCs between P3 and P14, but in only 1 of 11 IHCs at P16-P22. Potassium depolarization of efferent terminals caused IPSCs in 67% of IHCs at P3, in 100% at P7-P9, in 93% at P10-P12, but in only 40% at P13-P14 and in none of the IHCs tested between P16 and P22. Earlier work had shown by in situ hybridization that α9 mRNA is expressed in adult IHCs but that α10 mRNA disappears after the onset of hearing. In the present study, antibodies to α10 and to the associated calcium-dependent (SK2) potassium channel showed a similar developmental loss. The correlated expression of these gene products with functional innervation suggests that Alpha10 and SK2, but not Alpha9, are regulated by synaptic activity. Furthermore, this developmental knock-out of α10, but not α9, supports the hypothesis that functional nicotinic acetylcholine receptors in hair cells are heteromers containing both these subunits.
Fil:Katz, E. 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.
Source
J. Neurosci. 2004;24(36):7814-7820
Subject
α9α10 nAChR
Ca2+-activated K+ channel
Cholinergic
Efferent innervation
IHC
Mammalian cochlea
Neonatal development
Transient synapse
acetylcholine
calcium
calcium activated potassium channel
messenger RNA
nicotine
nicotinic receptor
nicotinic receptor alpha10 subunit
nicotinic receptor alpha9 subunit
potassium
receptor subunit
unclassified drug
Alpha10 gene
Alpha9 gene
animal cell
animal tissue
article
auditory stimulation
calcium transport
cochlea
Corti organ
depolarization
efferent nerve
gene
hair cell
hearing
in situ hybridization
ion current
knockout gene
newborn
nonhuman
postnatal development
priority journal
protein expression
rat
receptor potential
sensory nerve
signal transduction
sk2 gene
synapse
synaptogenesis
Acetylcholine
Action Potentials
Age Factors
Animals
Cochlea
Gene Expression Regulation, Developmental
Hair Cells, Inner
Hearing
Patch-Clamp Techniques
Potassium
Potassium Channels, Calcium-Activated
Protein Subunits
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic
Small-Conductance Calcium-Activated Potassium Channels
Synaptic Transmission
Access level
Open access
License
http://creativecommons.org/licenses/by/2.5/ar
Repository
Biblioteca Digital (UBA-FCEN)
Institution
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
OAI Identifier
snrd:HASH017dd417b1f13375d75b57e2