Phylogenetic Differences in Calcium Permeability of the Auditory Hair

LIPOVSEK M.; GI JUNG IM; FRANCHINI LF; PISCIOTTANO F.; KATZ E.; FUCHS PAUL A.; ELGOYHEN A.B.

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

NATL ACAD SCIENCES

Año: 2012 vol. 109 p. 4308 - 4313

0027-8424

The á9 and á10 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. Contrary to all nicotinic receptors which serve excitatory neurotransmission, the activation of á9á10 produces hyperpolarization of hair cells. An evolutionary analysis has shown that the á10 subunit shows signatures of positive selection only along the mammalian lineage, strongly suggesting the acquisition of a novel function. To establish if mammalian á9á10 receptors have acquired novel functional properties, as a consequence of this evolutionary pressure, we have compared the properties of rat and chicken recombinant and native á9á10 receptors. The main finding of the present work is that, in contrast to the high (pCa2+/pMonovalents ~ 10) Ca2+ permeability reported for rat á9á10 receptors, recombinant and native chicken á9á10 receptors have a much lower permeability (~ 2) to this cation, comparable to that of neuronal á4â2 receptors. Moreover, we show that, contrary to á10, á7 as well as á4 and â2 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 following á9á10 gating at the cholinergic-hair cell synapse. In addition, they suggest that high Ca2+ permeability of the á9á10 cholinergic nicotinic receptor might have evolved together with other features which have rendered a mammalian ear with an expanded high frequency sensitivity.