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

MARCELA LIPOVSEK; GI JUNG IM; LUCÍA F. FRANCHINI; FRANCISCO PISCIOTTANO; ELEONORA KATZ; PAUL A. FUCHS; ANA BELÉN ELGOYHEN

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2012 vol. 109 p. 4308 - 4313

0027-8424

The alpha9 and alpha10 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 alpha9alpha10 produces hyperpolarization of hair cells. An evolutionary analysis has shown that the alpha10 subunit exhibits signatures of positive selection only along the mammalian lineage, strongly suggesting the acquisition of a novel function. To establish whether mammalian alpha9alpha10 receptors have acquired novel functional properties as a consequence of this evolutionary pressure, we compared the properties of rat and chicken recombinant and native alpha9alpha10 receptors. Our main finding in the present work is that, in contrast to the high (pCa2+/pMonovalents around 10) Ca2+ permeability reported for rat alpha9alpha10 receptors, recombinant and native chicken alpha9alpha10 receptors have a much lower permeability (around 2) to this cation, comparable to that of neuronal alpha4beta2 receptors. Moreover, we show that, in contrast to alpha10, alpha7 as well as alpha4 and beta2 nicotinic subunits are under purifying selection in vertebrates, consistent with the conserved Ca2+ permeability reported across species. These results have important consequences for the activation of signaling cascades that lead to hyperpolarization of hair cells after alpha9alpha10 gating at the cholinergic hair cell synapse. In addition, they suggest that high Ca2+ permeability of the alpha9alpha10 cholinergic nicotinic receptor might have evolved together with other features that have given the mammalian ear an expanded high-frequency sensitivity.