Study of the adaptive evolution of the α9α10 cholinergic nicotinic receptor

IRINA MARCOVICH; PAOLA PLAZAS; MARCELA LIPOVSEK; ANA BELEN ELGOYHEN.

Huerta Grande, Córdoba, Argentina.

Congreso; XXIX CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2014

SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS

A great variety of nicotinic acetylcholine receptor (nAChR) subunits are expressed in different regions of the central nervous system. Thus, functional diversity across species can be achieved by the differential expression of alternative subunits. In contrast, cochlear hair cells only express α9 and α10 subunits, which form the heteromeric receptor that mediates efferent inhibition of vertebrate inner ear hair cells. Phylogenetic analysis has shown that mammalian α10 subunits have been under positive selection and acquired non-synonymous substitutions in their coding regions. We propose that these evolution-driven changes on a very conserved protein, are the only basis for functional diversity across species in the α9α10 nAChR. To test this hypothesis, we have compared the properties of rat, chicken and Xenopus tropicalis nAChRs formed by α9 and/or α10 subunits expressed in Xenopus laevis oocytes. Whereas chicken and X. tropicalis α10 subunits form functional homomeric receptors, rat α10 subunits are only functional when co-expressed with α9. Current-voltage curves show that rat α9α10 nAChR presents a lower degree of outward rectification compared to its avian counterpart, while amphibian α9α10 nAChR shows inward rectification, indicating differential channel properties. We propose that non-synonymous substitutions in the coding region of the mammalian α10 subunits are responsible for the differential functional properties between mammalian and non-mammalian α9α10 nAChRs.