FUNCTIONAL CONSEQUENCES OF ADAPTIVE EVOLUTION OF THE MAMMALIAN a9a10 NICOTINIC RECEPTOR

LIPOVSEK M; FRANCHINI L; KATZ E; MILLAR NS; FUCHS P; ELGOYHEN AB

Huerta Grande, Córdoba

Congreso; I Reunión Conjunta de Neurociencias (IRCN); 2009

Soc Argentina de Invest en Neurociencia

Functional Consequences of Adaptive evolution of the mammalian a9a10 nicotinic receptor. M. Lipovsek1, L. F. Franchini1, E. Katz1, Neil Millar2, P. A. Fuchs3 and A. B. Elgoyhen1. 1INGEBI – CONICET. Buenos Aires, Argentina, 2Department of Pharmacology, University Collage London, London, United Kingdom and 3Johns Hopkins University School of Medicine Baltimore, MD, USA. The a9a10 nicotinic acetylcholine receptor (nAChR) mediates efferent inhibition of cochlear hair cells in mammals and birds. This inhibition results from the activation of a calcium-dependent K+ current thought to depend on calcium entry through the activated nAChR. Sequence analysis of the CHRNA10 genes of different species revealed signs of adaptive evolution 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 the CHRNA10 gene. To test this hypothesis, we analyzed the properties of the recombinant chicken a9a10 receptor, using the two-electrode voltage-clamp technique in Xenopus laevis oocytes expressing these subunits. The sensitivity to ACh of the G. gallus receptor was lower than that of the R. norvegicus receptor (EC50=21.7±1.2 microM and 13.8±1.7 microM, respectively). The G. gallus a9a10 receptor shows a desensitization profile similar to that of the heteromeric a9a10 R. norvegicus nAChR. Interestingly, the oocyte’s endogenous calcium dependent chloride current strongly activated by the opening of the rat a9a10 nAChR  was not significantly activated by the G. gallus a9a10 nAChR, suggesting that the calcium permeability of the avian receptor is substantially lower than that of the mammalian receptor.              These results indicate that the mammalian a9a10 receptor has acquired new functional properties which are different from those of non-mammalian species. Supported by NIH, HHMI, UBA and ANPCyT.