Study of the adaptive evolution of the cholinergic nicotinic receptor 910

MARCOVICH I; LIPOVSEK M; PLAZAS P; ELGOYHEN AB

Congreso; XXIX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2014

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 several non-synonymous substitutions in its coding region. We propose that these acquired changes in the coding region of a very conserved protein, is the only basis for functional diversity across species in this nAChR. To test this hypothesis, we have compared the properties of rat, chicken and Xenopus tropicalis α9 and α10 receptors expressed in Xenopus laevis oocytes. Whereas chicken and X. tropicalis subunits form α10 homomeric receptors, mammalian α10 subunits are only functional when co-expressed with α9. Current-voltage curves show that rat α9α10 presents a lower degree of outward rectification compared to its avian counterpart, while amphibian α9α10 shows inward rectification, indicating differential channel properties. We propose that the non-synonymous substitutions in the coding region of the mammalian α10 are responsible for these differences in the biophysical properties of the nAChR.