Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor

• Autores: Lipovsek, M.; Im, G.J.; Franchini, L.F.; Pisciottano, F.; Katz, E.; Fuchs, P.A.; Elgoyhen, A.B.
• Año de publicación: 2012
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Proc. Natl. Acad. Sci. U. S. A. 2012;109(11):4308-4313
• Materia: Evolution; Ionotropic receptor; Ligand-gated channel; Outer hair cell; calcium ion; cation; cell receptor; nicotinic receptor alpha4beta2; animal cell; article; artificial chromosome; calcium transport; channel gating; chicken; hair cell; hyperpolarization; mammal; neurotransmission; nonhuman; phylogeny; priority journal; synapse; vertebrate; Acetylcholine; Animals; Calcium; Cell Membrane Permeability; Chickens; Evolution, Molecular; Hair Cells, Auditory; Humans; Likelihood Functions; Oocytes; Phylogeny; Protein Subunits; Rats; Receptors, Nicotinic; Recombinant Proteins; Xenopus laevis; Mammalia; Rattus; Vertebrata
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

The α9 and α10 cholinergic nicotinic receptor subunits assemble to form the receptor that mediates efferent inhibition of hair cell function within the auditory sensory organ, a mechanism thought to modulate the dynamic range of hearing. In contrast to all nicotinic receptors, which serve excitatory neurotransmission, the activation of α9α10 produces hyperpolarization of hair cells. An evolutionary analysis has shown that the α10 subunit exhibits signatures of positive selection only along the mammalian lineage, strongly suggesting the acquisition of a unique function. To establish whether mammalian α9α10 receptors have acquired distinct functional properties as a consequence of this evolutionary pressure, we compared the properties of rat and chicken recombinant and native α9α10 receptors. Our main finding in the present work is that, in contrast to the high (pCa 2+/pMonovalents ∼10) Ca 2+ permeability reported for rat α9α10 receptors, recombinant and native chicken α9α10 receptors have a much lower permeability (∼2) to this cation, comparable to that of neuronal α4β2 receptors. Moreover, we show that, in contrast to α10, α7 as well as α4 and β2 nicotinic subunits are under purifying selection in vertebrates, consistent with the conserved Ca 2+ permeability reported across species. These results have important consequences for the activation of signaling cascades that lead to hyperpolarization of hair cells after α9α10 gating at the cholinergic-hair cell synapse. In addition, they suggest that high Ca 2+ permeability of the α9α10 cholinergic nicotinic receptor might have evolved together with other features that have given the mammalian ear an expanded high-frequency sensitivity.
Fil:Lipovsek, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.