scholarly journals Distinct evolutionary trajectories of neuronal and hair cell nicotinic acetylcholine receptors

2019 ◽  
Author(s):  
Irina Marcovich ◽  
Marcelo J. Moglie ◽  
Agustín E. Carpaneto Freixas ◽  
Anabella P. Trigila ◽  
Lucia F. Franchini ◽  
...  
Keyword(s):  
Hair Cell ◽  
Functional Properties ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Expression Patterns ◽  
Nicotinic Acetylcholine ◽  
Coding Sequences ◽  
The Family ◽  
Evolutionary Trajectories ◽  
Cell Expression

ABSTRACTThe expansion and pruning of ion channel families has played a crucial role in the evolution of nervous systems. Remarkably, with a highly conserved vertebrate complement, nicotinic acetylcholine receptors (nAChRs) are unique among ligand-gated ion channels in that members of the family have distinct roles in synaptic transmission in non-overlapping domains, either in the nervous system, the inner ear hair cells or the neuromuscular junction. Here, we performed a comprehensive analysis of vertebrate nAChRs sequences, single cell expression patterns and comparative functional properties of receptors from three representative tetrapod species. We show that hair cell nAChRs underwent a distinct evolutionary trajectory to that of neuronal receptors. These were most likely shaped by different co-expression patterns and co-assembly rules of component subunits. Thus, neuronal nAChRs showed high degree of coding sequence conservation, coupled to greater co-expression variance and conservation of functional properties across tetrapod clades. In contrast, hair cell α9α10 nAChRs exhibited greater sequence divergence, narrow co-expression pattern and great variability of functional properties across species. These results point to differential substrates for random change within the family of gene paralogs that relate to the segregated roles of nAChRs in synaptic transmission.Significance statementOur work exploits several peculiarities of the family of vertebrate nicotinic acetylcholine receptors (nAChRs) to explore the evolutionary trajectories of a ligand-gated ion channel family. By performing a comprehensive comparative analysis of nAChR subunits coding sequences, single cell expression patterns and functional properties we found a contrasting evolutionary history between nAChRs with widespread expression in the nervous system compared to those with isolated expression in the inner ear. Evolutionary changes were focused on differences in co-expression and co-assembly patterns for the former and coding sequences in the latter. This multidisciplinary approach provides further insight into the evolutionary processes that shaped the nervous and sensory systems of extant animals.

scholarly journals Distinct Evolutionary Trajectories of Neuronal and Hair Cell Nicotinic Acetylcholine Receptors

2019 ◽  
Vol 37 (4) ◽  
pp. 1070-1089 ◽  
Author(s):  
Irina Marcovich ◽  
Marcelo J Moglie ◽  
Agustín E Carpaneto Freixas ◽  
Anabella P Trigila ◽  
Lucia F Franchini ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Hair Cell ◽  
Functional Properties ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Expression Patterns ◽  
Sequence Divergence ◽  
Nicotinic Acetylcholine ◽  
Evolutionary Trajectories ◽  
Cell Expression

Abstract The expansion and pruning of ion channel families has played a crucial role in the evolution of nervous systems. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels with distinct roles in synaptic transmission at the neuromuscular junction, the central and peripheral nervous system, and the inner ear. Remarkably, the complement of nAChR subunits has been highly conserved along vertebrate phylogeny. To ask whether the different subtypes of receptors underwent different evolutionary trajectories, we performed a comprehensive analysis of vertebrate nAChRs coding sequences, mouse single-cell expression patterns, and comparative functional properties of receptors from three representative tetrapod species. We found significant differences between hair cell and neuronal receptors that were most likely shaped by the differences in coexpression patterns and coassembly rules of component subunits. Thus, neuronal nAChRs showed high degree of coding sequence conservation, coupled to greater coexpression variance and conservation of functional properties across tetrapod clades. In contrast, hair cell α9α10 nAChRs exhibited greater sequence divergence, narrow coexpression pattern, and great variability of functional properties across species. These results point to differential substrates for random change within the family of gene paralogs that relate to the segregated roles of nAChRs in synaptic transmission.

scholarly journals The Hair Cell α9α10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family

2021 ◽  
Vol 15 ◽  
Author(s):  
Marcela Lipovsek ◽  
Irina Marcovich ◽  
Ana Belén Elgoyhen
Keyword(s):  
Hair Cell ◽  
Nicotinic Acetylcholine Receptors ◽  
Hair Cells ◽  
Acetylcholine Receptors ◽  
Nicotinic Receptors ◽  
Sequence Divergence ◽  
Receptor Subtype ◽  
Nicotinic Acetylcholine ◽  
Functional Consequences ◽  
Mechanosensory Hair Cells

Nicotinic acetylcholine receptors (nAChRs) are a subfamily of pentameric ligand-gated ion channels with members identified in most eumetazoan clades. In vertebrates, they are divided into three subgroups, according to their main tissue of expression: neuronal, muscle and hair cell nAChRs. Each receptor subtype is composed of different subunits, encoded by paralogous genes. The latest to be identified are the α9 and α10 subunits, expressed in the mechanosensory hair cells of the inner ear and the lateral line, where they mediate efferent modulation. α9α10 nAChRs are the most divergent amongst all nicotinic receptors, showing marked differences in their degree of sequence conservation, their expression pattern, their subunit co-assembly rules and, most importantly, their functional properties. Here, we review recent advances in the understanding of the structure and evolution of nAChRs. We discuss the functional consequences of sequence divergence and conservation, with special emphasis on the hair cell α9α10 receptor, a seemingly distant cousin of neuronal and muscle nicotinic receptors. Finally, we highlight potential links between the evolution of the octavolateral system and the extreme divergence of vertebrate α9α10 receptors.

scholarly journals Nicotinic acetylcholine receptor-mediated responses in medial vestibular and prepositus hypoglossi nuclei neurons showing distinct neurotransmitter phenotypes

2016 ◽  
Vol 115 (5) ◽  
pp. 2649-2657 ◽  
Author(s):  
Yue Zhang ◽  
Yuchio Yanagawa ◽  
Yasuhiko Saito
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Vestibular Nucleus ◽  
Expression Patterns ◽  
Muscarinic Acetylcholine Receptors ◽  
Medial Vestibular Nucleus ◽  
Nicotinic Acetylcholine ◽  
Decay Times ◽  
Prepositus Hypoglossi ◽  
Α7 Nachrs

Cholinergic transmission in both the medial vestibular nucleus (MVN) and prepositus hypoglossi nucleus (PHN) plays an important role in horizontal eye movements. We previously demonstrated that the current responses mediated via nicotinic acetylcholine receptors (nAChRs) were larger than those mediated via muscarinic acetylcholine receptors (mAChRs) in cholinergic MVN and PHN neurons that project to the cerebellum. In this study, to clarify the predominant nAChR responses and the expression patterns of nAChRs in MVN and PHN neurons that exhibit distinct neurotransmitter phenotypes, we identified cholinergic, inhibitory, and glutamatergic neurons using specific transgenic rats and investigated current responses to the application of acetylcholine (ACh) using whole cell recordings in brain stem slices. ACh application induced larger nAChR-mediated currents than mAChR-mediated currents in every neuronal phenotype. In the presence of an mAChR antagonist, we found three types of nAChR-mediated currents that exhibited different rise and decay times and designated these as fast (F)-, slow (S)-, and fast and slow (FS)-type currents. F-type currents were the predominant response in inhibitory MVN neurons, whereas S-type currents were observed in the majority of glutamatergic MVN and PHN neurons. No dominant response type was observed in cholinergic neurons. Pharmacological analyses revealed that the F-, S-, and FS-type currents were mainly mediated by α7, non-α7, and both α7 and non-α7 nAChRs, respectively. These findings suggest that cholinergic responses in the major neuronal populations of the MVN and PHN are predominantly mediated by nAChRs and that the expression of α7 and non-α7 nAChRs differ among the neuronal phenotypes.

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