Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells

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 na...

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Autores principales:	Gómez Casati, María Eugenia, Katz, Eleonora
Publicado:	2005
Materias:	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 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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223751_v566_n1_p103_GomezCasati http://hdl.handle.net/20.500.12110/paper_00223751_v566_n1_p103_GomezCasati
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00223751_v566_n1_p103_GomezCasati
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spelling	paper:paper_00223751_v566_n1_p103_GomezCasati2023-06-08T14:50:27Z Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells Gómez Casati, María Eugenia Katz, Eleonora 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 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. Fil:Gómez-Casati, M.E. 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. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223751_v566_n1_p103_GomezCasati http://hdl.handle.net/20.500.12110/paper_00223751_v566_n1_p103_GomezCasati
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Gómez Casati, María Eugenia Katz, Eleonora Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
topic_facet	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
description	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.
author	Gómez Casati, María Eugenia Katz, Eleonora
author_facet	Gómez Casati, María Eugenia Katz, Eleonora
author_sort	Gómez Casati, María Eugenia
title	Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
title_short	Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
title_full	Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
title_fullStr	Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
title_full_unstemmed	Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
title_sort	biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells
publishDate	2005
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223751_v566_n1_p103_GomezCasati http://hdl.handle.net/20.500.12110/paper_00223751_v566_n1_p103_GomezCasati
work_keys_str_mv	AT gomezcasatimariaeugenia biophysicalandpharmacologicalcharacterizationofnicotiniccholinergicreceptorsinratcochlearinnerhaircells AT katzeleonora biophysicalandpharmacologicalcharacterizationofnicotiniccholinergicreceptorsinratcochlearinnerhaircells
_version_	1768544028373024768

Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells

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