CONICET | Buscador de Institutos y Recursos Humanos

The a9a10 nicotinic acetylcholine receptor (nAChR) mediates efferentinhibition of cochlear hair cells in mammals and birds. This inhibition resultsfrom activation of a calcium-dependent potassium current thought to depend oncalcium entry through the activated nAChR. Sequence analysis of the CHRNA10genes (but not of CHRNA9) of different species revealed signs of adaptiveevolution in the mammalian lineage (Franchini and Elgoyhen, 2006). Therefore,one could propose that the mammalian a9a10 receptor (i.e., from R. norvegicus)would have functional properties different from those of the avian receptor (i.e.,from G. gallus) as a result of specific, non-synonymous substitutions within theCHRNA10 gene.To begin to test this hypothesis, we analyzed the properties of therecombinant chicken a9a10 receptor, using the two-electrode voltage-clamptechnique in Xenopus laevis oocytes expressing these subunits. The sensitivity toACh of the G. gallus receptor was lower than that of the R. norvegicus receptor(EC50=21.7±1.2mM and 13.8±1.7mM, respectively). In addition, the G. gallusa9a10 receptor did not desensitize significantly, in a manner similar to that ofthe homomeric a9 from rat, and different to the strong desensitization of theheteromeric a9a10 R. norvegicus receptor. Perhaps most notably, the oocytesendogenous calcium dependent chloride current stimulated by rat a9a10 was notactivated by the G. gallus a9a10 receptors, suggesting that calcium permeabilityof the avian receptor is substantially lower than that of the mammalian receptor.These results indicate that the mammalian a9a10 receptor has acquirednew functional properties which are different from those of non-mammalianspecies. This most likely results from the positive selection of non-synonymoussubstitutions in the a10 subunit during the evolution of this lineage