Comparative study of the functional properties of cochlear and neuronal cholinergic nicotinic receptors across different tetrapod species

MARCOVICH I; LIPOVSEK M; PLAZAS P; ELGOYHEN AB

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Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2015

Nicotinic acetylcholine receptors (nAChRs) are members of the Cys loop superfamily of ligand-gated ion channels. They can be classified into three groups: muscle, neuronal and epithelial. The muscle receptor is assembled from α1,β1,δ and γ/ε subunits, neuronal receptors from the combination of different α2 ?α8 and β2 ?β4 subunits and the epithelial receptor of cochlear hair cells from α9 and α10 subunits. Unlike the rest of nAChR subunits, phylogenetic analysis has shown that mammalian α10 have been under positive selection and acquired several non-synonymous substitutions in its coding region. We propose that these acquired changes is the basis for functional diversity across species in the case a9a10 nAChR compared to neuronal nAChRs which can assemble from the wide variety of subunits expressed in the central nervous system. Thus, we hypothesis that the biophysical properties of the α9α10 nAChRs should vary across different vertebrate species, while those of neuronal nAChRs properties should be conserved. We have compared the properties of recombinant rat, chicken and Xenopus tropicalis α9α10 receptors and those of α7 neuronal receptors expressed in Xenopus laevis oocytes. Whereas rat, chicken and X. tropicalis α9α10 nAChRs differ in their desensitization rate, Ca2+ permeability, Ca2+ modulation and current-voltage relationship, neuronal α7 nAChR exhibit similar channel properties. These results suggest that the peculiar evolutionary history of the α10 subunit could account for thedifferential functional properties across species of the a9a10 nAChR.