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Abstract:

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 α9 and α10 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 (PCa/PNa = 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 α9α10 nAChR, reinforcing the hypothesis that the functional nAChR at the olivocochlear efferent-IHC synapse is composed of both the α19 and α10 subunits. © The Physiological Society 2005.

Registro:

Documento: Artículo
Título:Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
Autor:Gómez-Casati, M.E.; Fuchs, P.A.; Elgoyhen, A.B.; Katz, E.
Filiación:Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Téchnicas, Universidad de Buenos Aires, Buenos Aires, Argentina
Cochlear Neurotransmission Laboratory, Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Departamento de Fisiología, Biología Molecular y Cellular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:acetylcholine; barium ion; bicuculline; calcium ion; magnesium ion; nicotine; nicotinic receptor; strychnine; tropisetron; animal cell; animal experiment; animal tissue; article; cochlea; concentration response; controlled study; Corti organ; electrophysiology; evoked response; extracellular calcium; hair cell; hearing; IC 50; inhibition kinetics; ion current; nonhuman; priority journal; rat; receptor intrinsic activity; synapse; Article; calcium current; calcium transport; cell membrane permeability; channel gating; Corti organ; desensitization; inhibitory postsynaptic potential; inner hair cell; synaptic transmission; Action Potentials; Adaptation, Physiological; Aging; Animals; Animals, Newborn; Auditory Pathways; Hair Cells, Inner; Homeostasis; Long-Term Potentiation; Neural Inhibition; Neuronal Plasticity; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Synapses; Synaptic Transmission
Año:2005
Volumen:566
Número:1
Página de inicio:103
Página de fin:118
DOI: http://dx.doi.org/10.1113/jphysiol.2005.087155
Título revista:Journal of Physiology
Título revista abreviado:J. Physiol.
ISSN:00223751
CODEN:JPHYA
CAS:acetylcholine, 51-84-3, 60-31-1, 66-23-9; barium ion, 22541-12-4; bicuculline, 485-49-4; calcium ion, 14127-61-8; magnesium ion, 22537-22-0; nicotine, 54-11-5; strychnine, 1421-86-9, 57-24-9; tropisetron, 89565-68-4; Receptors, Nicotinic
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223751_v566_n1_p103_GomezCasati

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Citas:

---------- APA ----------
Gómez-Casati, M.E., Fuchs, P.A., Elgoyhen, A.B. & Katz, E. (2005) . Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells. Journal of Physiology, 566(1), 103-118.
http://dx.doi.org/10.1113/jphysiol.2005.087155
---------- CHICAGO ----------
Gómez-Casati, M.E., Fuchs, P.A., Elgoyhen, A.B., Katz, E. "Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells" . Journal of Physiology 566, no. 1 (2005) : 103-118.
http://dx.doi.org/10.1113/jphysiol.2005.087155
---------- MLA ----------
Gómez-Casati, M.E., Fuchs, P.A., Elgoyhen, A.B., Katz, E. "Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells" . Journal of Physiology, vol. 566, no. 1, 2005, pp. 103-118.
http://dx.doi.org/10.1113/jphysiol.2005.087155
---------- VANCOUVER ----------
Gómez-Casati, M.E., Fuchs, P.A., Elgoyhen, A.B., Katz, E. Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells. J. Physiol. 2005;566(1):103-118.
http://dx.doi.org/10.1113/jphysiol.2005.087155