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

I. MARCOVICH; M. LIPOVSEK; P. PLAZAS; AB. ELGOYHEN

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Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigacion en Neurociencias; 2015

Nicotinic acetylcholine receptors (nAChRs) are members of the Cys loop superfamily of ligand-gated ion channels. They can be classified into muscle, neuronal and epithelial. The neuronal receptors assemble 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 has 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 of α9α10 compared to neuronal nAChRs, which can assemble from the wide variety of subunits expressed in the central nervous system. Thus, we hypothesize that the biophysical properties of the α9α10 nAChRs should vary across different vertebrate species, but those of neuronal nAChRs should be conserved. We compared the properties of recombinant rat, chicken and frog α9α10 and those of α7 neuronal receptors expressed in Xenopus laevis oocytes. Whereas rat, chicken and frog 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 resulted in differential functional properties of the α9α10 nAChR across species.