title: Developmental regulation of nicotinic synapses on cochlear inner hair cells.
abstract: 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 alpha9 and alpha10 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 alpha9 mRNA is expressed in adult IHCs but that alpha10 mRNA disappears after the onset of hearing. In the present study, antibodies to alpha10 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 alpha10, but not alpha9, supports the hypothesis that functional nicotinic acetylcholine receptors in hair cells are heteromers containing both these subunits.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad de Buenos Aires (UBA), Argentina.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Katz
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Elgoyhen
authors.forename: María E
authors.initials: ME
authors.lastname: Gómez-Casati
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vetter
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fuchs
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Glowatzki
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D003051:Cochlea / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism* / Q000502:physiology; D006309:Hearing / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: C470699:Chrna10 protein, rat; C498541:Chrna9 protein, rat; C496899:Kcnn2 protein, rat; D024681:Potassium Channels, Calcium-Activated; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D051640:Small-Conductance Calcium-Activated Potassium Channels; D000109:Acetylcholine; D011188:Potassium