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Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit

The α9α10 nicotinic acetylcholine receptor (nAChR) plays a fundamental role in inner ear physiology. It mediates synaptic transmission between efferent olivocochlear fibers that descend from the brainstem and hair cells of the auditory sensory epithelium. The α9 and α10 subunits have undergone a dis...

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Autores principales: Moglie, Marcelo J., Marcovich, Irina, Corradi, Jeremías, Carpaneto Freixas, Agustín E., Gallino, Sofía, Plazas, Paola V., Bouzat, Cecilia, Lipovsek, Marcela, Elgoyhen, Ana Belén
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892445/
https://www.ncbi.nlm.nih.gov/pubmed/33613194
http://dx.doi.org/10.3389/fnmol.2021.639720
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author Moglie, Marcelo J.
Marcovich, Irina
Corradi, Jeremías
Carpaneto Freixas, Agustín E.
Gallino, Sofía
Plazas, Paola V.
Bouzat, Cecilia
Lipovsek, Marcela
Elgoyhen, Ana Belén
author_facet Moglie, Marcelo J.
Marcovich, Irina
Corradi, Jeremías
Carpaneto Freixas, Agustín E.
Gallino, Sofía
Plazas, Paola V.
Bouzat, Cecilia
Lipovsek, Marcela
Elgoyhen, Ana Belén
author_sort Moglie, Marcelo J.
collection PubMed
description The α9α10 nicotinic acetylcholine receptor (nAChR) plays a fundamental role in inner ear physiology. It mediates synaptic transmission between efferent olivocochlear fibers that descend from the brainstem and hair cells of the auditory sensory epithelium. The α9 and α10 subunits have undergone a distinct evolutionary history within the family of nAChRs. Predominantly in mammalian vertebrates, the α9α10 receptor has accumulated changes at the protein level that may ultimately relate to the evolutionary history of the mammalian hearing organ. In the present work, we investigated the responses of α9α10 nAChRs to choline, the metabolite of acetylcholine degradation at the synaptic cleft. Whereas choline is a full agonist of chicken α9α10 receptors it is a partial agonist of the rat receptor. Making use of the expression of α9α10 heterologous receptors, encompassing wild-type, heteromeric, homomeric, mutant, chimeric, and hybrid receptors, and in silico molecular docking, we establish that the mammalian (rat) α10 nAChR subunit underscores the reduced efficacy of choline. Moreover, we show that whereas the complementary face of the α10 subunit does not play an important role in the activation of the receptor by ACh, it is strictly required for choline responses. Thus, we propose that the evolutionary changes acquired in the mammalian α9α10 nAChR resulted in the loss of choline acting as a full agonist at the efferent synapse, without affecting the triggering of ACh responses. This may have accompanied the fine-tuning of hair cell post-synaptic responses to the high-frequency activity of efferent medial olivocochlear fibers that modulate the cochlear amplifier.
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spelling pubmed-78924452021-02-20 Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit Moglie, Marcelo J. Marcovich, Irina Corradi, Jeremías Carpaneto Freixas, Agustín E. Gallino, Sofía Plazas, Paola V. Bouzat, Cecilia Lipovsek, Marcela Elgoyhen, Ana Belén Front Mol Neurosci Neuroscience The α9α10 nicotinic acetylcholine receptor (nAChR) plays a fundamental role in inner ear physiology. It mediates synaptic transmission between efferent olivocochlear fibers that descend from the brainstem and hair cells of the auditory sensory epithelium. The α9 and α10 subunits have undergone a distinct evolutionary history within the family of nAChRs. Predominantly in mammalian vertebrates, the α9α10 receptor has accumulated changes at the protein level that may ultimately relate to the evolutionary history of the mammalian hearing organ. In the present work, we investigated the responses of α9α10 nAChRs to choline, the metabolite of acetylcholine degradation at the synaptic cleft. Whereas choline is a full agonist of chicken α9α10 receptors it is a partial agonist of the rat receptor. Making use of the expression of α9α10 heterologous receptors, encompassing wild-type, heteromeric, homomeric, mutant, chimeric, and hybrid receptors, and in silico molecular docking, we establish that the mammalian (rat) α10 nAChR subunit underscores the reduced efficacy of choline. Moreover, we show that whereas the complementary face of the α10 subunit does not play an important role in the activation of the receptor by ACh, it is strictly required for choline responses. Thus, we propose that the evolutionary changes acquired in the mammalian α9α10 nAChR resulted in the loss of choline acting as a full agonist at the efferent synapse, without affecting the triggering of ACh responses. This may have accompanied the fine-tuning of hair cell post-synaptic responses to the high-frequency activity of efferent medial olivocochlear fibers that modulate the cochlear amplifier. Frontiers Media S.A. 2021-02-05 /pmc/articles/PMC7892445/ /pubmed/33613194 http://dx.doi.org/10.3389/fnmol.2021.639720 Text en Copyright © 2021 Moglie, Marcovich, Corradi, Carpaneto Freixas, Gallino, Plazas, Bouzat, Lipovsek and Elgoyhen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Moglie, Marcelo J.
Marcovich, Irina
Corradi, Jeremías
Carpaneto Freixas, Agustín E.
Gallino, Sofía
Plazas, Paola V.
Bouzat, Cecilia
Lipovsek, Marcela
Elgoyhen, Ana Belén
Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit
title Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit
title_full Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit
title_fullStr Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit
title_full_unstemmed Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit
title_short Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit
title_sort loss of choline agonism in the inner ear hair cell nicotinic acetylcholine receptor linked to the α10 subunit
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892445/
https://www.ncbi.nlm.nih.gov/pubmed/33613194
http://dx.doi.org/10.3389/fnmol.2021.639720
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