INVESTIGADORES
BOUZAT Cecilia Beatriz
artículos
Título:
Loss of choline agonism in the inner ear hair cell nicotinic acetylcholine receptor linked to the alpha10 subunit
Autor/es:
MOGLIE, M.J.; MARCOVICH, I.; CORRADI, J.; CARPANETO FREIXAS, A.E.; GALLINO, S.; PLAZAS, P.V.; BOUZAT, C.B.; LIPOVSEK, M.; ELGOYHEN, A.B.
Revista:
Frontiers in Molecular Neuroscience
Editorial:
Frontiers Media S.A.
Referencias:
Año: 2021 vol. 14 p. 1 - 14
Resumen:
The alpha9alpha10 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 alpha9 and alpha10 subunits have undergone a distinct evolutionary history within the family of nAChRs. Predominantly in mammalian vertebrates, the alpha9alpha10 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 alpha9alpha10 nAChRs to choline, the metabolite of acetylcholine degradation at the synaptic cleft. Whereas choline is a full agonist of chicken alpha9alpha10 receptors it is a partial agonist of the rat receptor. Making use of the expression of alpha9alpha10 heterologous receptors, encompassing wild-type, heteromeric, homomeric, mutant, chimeric, and hybrid receptors, and in silico molecular docking, we establish that the mammalian(rat) alpha10 nAChR subunit underscores the reduced efficacy of choline. Moreover, we show that whereas the complementary face of the alpha10 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 alpha9alpha10 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.