Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor
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...
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todo:paper_00278424_v109_n11_p4308_Lipovsek2023-10-03T14:38:06Z Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor Lipovsek, M. Im, G.J. Franchini, L.F. Pisciottano, F. Katz, E. Fuchs, P.A. Elgoyhen, A.B. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00278424_v109_n11_p4308_Lipovsek |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Lipovsek, M. Im, G.J. Franchini, L.F. Pisciottano, F. Katz, E. Fuchs, P.A. Elgoyhen, A.B. Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Lipovsek, M. Im, G.J. Franchini, L.F. Pisciottano, F. Katz, E. Fuchs, P.A. Elgoyhen, A.B. |
| author_facet |
Lipovsek, M. Im, G.J. Franchini, L.F. Pisciottano, F. Katz, E. Fuchs, P.A. Elgoyhen, A.B. |
| author_sort |
Lipovsek, M. |
| title |
Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor |
| title_short |
Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor |
| title_full |
Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor |
| title_fullStr |
Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor |
| title_full_unstemmed |
Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor |
| title_sort |
phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor |
| url |
http://hdl.handle.net/20.500.12110/paper_00278424_v109_n11_p4308_Lipovsek |
| work_keys_str_mv |
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| _version_ |
1807320448967376896 |