期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：11
页码：4308-4313
DOI：10.1073/pnas.1115488109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The 9 and 10 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 910 produces hyperpolarization of hair cells. An evolutionary analysis has shown that the 10 subunit exhibits signatures of positive selection only along the mammalian lineage, strongly suggesting the acquisition of a unique function. To establish whether mammalian 910 receptors have acquired distinct functional properties as a consequence of this evolutionary pressure, we compared the properties of rat and chicken recombinant and native 910 receptors. Our main finding in the present work is that, in contrast to the high (pCa2+/pMonovalents [~]10) Ca2+ permeability reported for rat 910 receptors, recombinant and native chicken 910 receptors have a much lower permeability ([~]2) to this cation, comparable to that of neuronal 4{beta}2 receptors. Moreover, we show that, in contrast to 10, 7 as well as 4 and {beta}2 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 910 gating at the cholinergic-hair cell synapse. In addition, they suggest that high Ca2+ permeability of the 910 cholinergic nicotinic receptor might have evolved together with other features that have given the mammalian ear an expanded high-frequency sensitivity.
