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This Article Full Text Full Text (PDF) All Versions of this Article: 566/1/103    most recent jphysiol.2005.087155v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gómez-Casati, M. E. Articles by Katz, E. Search for Related Content PubMed PubMed Citation Articles by Gómez-Casati, M. E. Articles by Katz, E.

¹ Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas – Universidad de Buenos Aires, Buenos Aires, Argentina
² Cochlear Neurotransmission Laboratory, Center for Hearing and Balance, Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
³ Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

Before the onset of hearing, a transient efferent innervation is found on inner hair cells (IHCs). This synapse is inhibitory and mediated by a nicotinic cholinergic receptor (nAChR) probably formed by the 9 and 10 subunits. We analysed the pharmacological and biophysical characteristics of the native nAChR using whole-cell recordings from IHCs in acutely excised apical turns of the rat organ of Corti. Nicotine did not activate but rather blocked the acetylcholine (ACh)-evoked currents with an IC₅₀ of 1 ± 0.1 µM. Antagonists of non-cholinergic receptors such as strychnine, bicuculline and ICS-205930 blocked ACh-evoked responses with an IC₅₀ of 8.6 ± 0.8 nM, 59 ± 4 nM and 0.30 ± 0.02 µM, respectively. The IHC nAChR was both permeable to (P_Ca/P_Na = 8 ± 0.9) and modulated by external Ca²⁺. ACh-evoked currents were potentiated by Ca²⁺ up to 500 µM but were reduced by higher concentrations of this cation. Ba²⁺ mimicked the effects of Ca²⁺ whereas Mg²⁺ only blocked these currents. In addition, elevation of extracellular Ca²⁺ reduced the amplitude of spontaneous synaptic currents without affecting their time course. The receptor had an EC₅₀ for ACh of 60.7 ± 2.8 µM in 0.5 mM Ca²⁺. In the absence of Ca²⁺, the EC₅₀ for ACh increased, suggesting that potentiation by Ca²⁺ involves changes in the apparent affinity for the agonist. These pharmacological and biophysical characteristics of the IHC nAChR closely resemble those of the recombinant 910 nAChR, reinforcing the hypothesis that the functional nAChR at the olivocochlear efferent–IHC synapse is composed of both the 9 and 10 subunits.

(Received 23 March 2005; accepted after revision 21 April 2005; first published online 28 April 2005)
Corresponding author Eleonora Katz: INGEBI, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina. Email: ekatz{at}dna.uba.ar

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