Unraveling the evolutionary history of nicotinic cholinergic receptors subunits

IRINA MARCOVICH; PAOLA PLAZAS; MARCELA LIPOVSEK; ANA BELÉN ELGOYHEN; LUCIA FRANCHINI

Ciudad Autónoma de Buenos Aires

Congreso; 2nd FALAN Congress; 2016

Nicotinic acetylcholine receptors (nAChRs) are members of the pentameric ligand-gated ion channel superfamily. In vertebrates, three types of nAChRs can be distinguished: muscle, neuronal and epithelial. Neuronal nAChRs can assemble from a variety of subunits: a2?a8 and b2?b4, whereas the epithelial nAChRs expressed in the inner ear are assembled from a9 and a10 subunits. Evolutionary analysis has shown that mammalian a10, but not other nAChR subunits, has been under positive selection and acquired several non-synonymous substitutions in its coding region. We propose that these acquired changes are the basis for functional diversity across species in the case of a9a10 compared to neuronal nAChRs, which can assemble from the wide variety of subunits. We hypothesize that the biophysical properties of the a9a10 nAChRs should vary across different vertebrate species, but those of neuronal nAChRs should be conserved. We studied the functional properties of recombinant rat, chicken and frog a9a10 and those of a7 and a4b2 neuronal receptors expressed in Xenopus laevis oocytes. a9a10 nAChRs from the three species present differences in their desensitization rate, Ca2+ permeability and modulation and current-voltage curves. In contrast, in the case of neuronal receptors these properties are similar. These results suggest that the differential functional properties of the a9a10 nAChRs across species resulted from the peculiar evolutionary process to which mammalian a10 was subjected.