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 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 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.

Differential Modulation of Nicotinic Acetylcholine Receptor Subtypes and Synaptic Transmission in Chick Sympathetic Ganglia by PGE2

2001 ◽  
Vol 85 (6) ◽  
pp. 2498-2508 ◽  
Author(s):  
Chuang Du ◽  
Lorna W. Role
Keyword(s):  
Synaptic Transmission ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuronal Excitability ◽  
Sympathetic Neuron ◽  
Sympathetic Ganglia ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Nicotinic Acetylcholine ◽  
Nachr Subtype

The diversity of neuronal nicotinic acetylcholine receptors (nAChRs) is likely an important factor in the modulation of synaptic transmission by acetylcholine and nicotine. We have tested whether postsynaptic nAChRs are modulated in a subtype-specific manner by prostaglandin E2(PGE2), a regulator of neuronal excitability in both the central and peripheral nervous systems, and examined the effects of PGE2 on nicotinic transmission. Somatodendritic nAChRs in chick lumbar sympathetic ganglia include four nAChR subtypes distinguished on the basis of conductance and kinetic profile. Nanomolar PGE2 applied to the extrapatch membrane differentially regulates opening probability (Po), frequency and the opening duration of each nAChR channel subtype in cell-attached patches. PGE2 decreases the Po of the predominant nAChR subtype (36 pS) and significantly increases Po and open duration of the 23 pS subtype. The 23 pS subtype is gated by the α7-selective agonist choline, and choline-gated currents are inhibited by α-bungarotoxin. To examine whether PGE2modulates nAChRs at synaptic sites, we studied the effects of PGE2 on amplitude and decay of synaptic currents in visceral motoneuron-sympathetic neuron co-cultures. PGE2 significantly decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), consistent with the predominant inhibition by PGE2 of all but the 23 pS subtype. The time constant of mEPSCs at PGE2-treated synapses is prolonged, which is also consistent with an increased contribution of the longer open duration of the 23 pS nAChR subtype with PGE2 treatment. To examine the presynaptic effect of PGE2, nanomolar nicotine was used. Nicotine induces facilitation of synaptic transmission by increasing mEPSC frequency, an action thought to involve presynaptic, α7-containing nAChRs. In the presence of PGE2, nicotine-induced synaptic facilitation persists. Thus the net effect of PGE2 is to alter the profile of nAChRs contributing to synaptic transmission from larger conductance, briefer opening channels to smaller conductance, longer opening events. This subtype-specific modulation of nAChRs by PGE2 may provide a mechanism for selective activation and suppression of synaptic pathways mediated by different nAChR subtype(s) at both pre- and postsynaptic sites.

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