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[摘要]：The alpha 9 and alpha 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 alpha 9 alpha 10 produces hyperpolarization of hair cells. An evolutionary analysis has shown that the alpha 10 subunit exhibits signatures of positive selection only along the mammalian lineage, strongly suggesting the acquisition of a unique function. To establish whether mammalian alpha 9 alpha 10 receptors have acquired distinct functional properties as a consequence of this evolutionary pressure, we compared the properties of rat and chicken recombinant and native alpha 9 alpha 10 receptors. Our main finding in the present work is that, in contrast to the high (pCa(2+)/pMonovalents similar to 10) Ca2+ permeability reported for rat alpha 9 alpha 10 receptors, recombinant and native chicken alpha 9 alpha 10 receptors have a much lower permeability (similar to 2) to this cation, comparable to that of neuronal alpha 4 beta 2 receptors. Moreover, we show that, in contrast to alpha 10, alpha 7 as well as alpha 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 alpha 9 alpha 10 gating at the cholinergic-hair cell synapse. In addition, they suggest that high Ca2+ permeability of the alpha 9 alpha 10 cholinergic nicotinic receptor might have evolved together with other features that have given the mammalian ear an expanded high-frequency sensitivity. |
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