Cholinergic transmission in C . elegans : Functions, diversity, and maturation of ACh‐activated ion channels

2020 ◽  
Author(s):  
Millet Treinin ◽  
Yishi Jin
Keyword(s):  
Ion Channels ◽  
Cholinergic Transmission ◽  
C Elegans

scholarly journals Cholinergic signalling at the body wall neuromuscular junction couples to distal inhibition of feeding in C. elegans

2021 ◽  
Author(s):  
Patricia G. Izquierdo ◽  
Thibana Thisainathan ◽  
James H. Atkins ◽  
Christian J. Lewis ◽  
John E.H. Tattersall ◽  
...  
Keyword(s):  
Body Wall ◽  
Neuromuscular Junctions ◽  
Model Organism ◽  
Inhibitory Effect ◽  
The Body ◽  
Body Wall Muscle ◽  
Cholinergic Transmission ◽  
Systematic Screening ◽  
C Elegans ◽  
Pharyngeal Pumping

AbstractComplex biological functions within organisms are frequently orchestrated by systemic communication between tissues. In the model organism C. elegans, the pharyngeal and body wall neuromuscular junctions are two discrete structures that control feeding and locomotion, respectively. These distinct tissues are controlled by separate, well-defined neural circuits. Nonetheless, the emergent behaviours, feeding and locomotion, are coordinated to guarantee the efficiency of food intake. We show that pharmacological hyperactivation of cholinergic transmission at the body wall muscle reduces the rate of pumping behaviour. This was evidenced by a systematic screening of the cholinesterase inhibitor aldicarb’s effect on the rate of pharyngeal pumping on food in mutant worms. The screening revealed that the key determinant of the inhibitory effect of aldicarb on pharyngeal pumping is the L-type nicotinic acetylcholine receptor expressed in body wall muscle. This idea was reinforced by the observation that selective hyperstimulation of the body wall muscle L-type receptor by the agonist levamisole inhibited pumping. Overall, our results reveal that body wall cholinergic transmission controls locomotion and simultaneously couples a distal inhibition of feeding.

scholarly journals Deorphanisation of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning

2020 ◽  
Author(s):  
Julia Morud ◽  
Iris Hardege ◽  
He Liu ◽  
Taihong Wu ◽  
Swaraj Basu ◽  
...  
Keyword(s):  
Ion Channels ◽  
Biogenic Amine ◽  
Pathogenic Bacteria ◽  
Serotonin Receptor ◽  
Neuronal Function ◽  
Olfactory Conditioning ◽  
C Elegans ◽  
Neuronal Processes ◽  
Amine Neurotransmitters ◽  
Gated Ion Channels

SummaryPentameric ligand-gated ion channels (LGCs) play conserved, critical roles in fast synaptic transmission, and changes in LGC expression and localisation are thought to underlie many forms of learning and memory. The C. elegans genome encodes a large number of LGCs without a known ligand or function. Here, we deorphanize five members of a family of Cys-loop LGCs by characterizing their diverse functional properties that are activated by biogenic amine neurotransmitters. To analyse the neuronal function of these LGCs, we show that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning. lgc-50 mutants show a specific defect in learned olfactory avoidance of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the expression of LGC-50 in neuronal processes is enhanced by olfactory conditioning; thus, the regulated expression of these receptors at synapses appears to represent a molecular cornerstone of the learning mechanism.

scholarly journals Dopamine negatively modulates the NCA ion channels in C. elegans

PLoS Genetics ◽  
2017 ◽  
Vol 13 (10) ◽  
pp. e1007032 ◽  
Author(s):  
Irini Topalidou ◽  
Kirsten Cooper ◽  
Laura Pereira ◽  
Michael Ailion
Keyword(s):  
Ion Channels ◽  
C Elegans

scholarly journals EGL-19 and EXP-2 Ion Channels Modelling within C. Elegans Pharyngeal Muscle Cell Allows Reproduction of CA2+ Driven Action Potentials, Both Single Events and Trains

2017 ◽  
Author(s):  
Andrey Yu. Palyanov ◽  
Khristina V. Samoilova ◽  
Natalia V. Palyanova
Keyword(s):  
Ion Channels ◽  
Muscle Cell ◽  
Action Potentials ◽  
Computational Models ◽  
Signal Transmission ◽  
Open Science ◽  
Time Profile ◽  
Simulation Environment ◽  
Pharyngeal Muscle ◽  
C Elegans

One of the current problems at the interface between neuroscience, biophysics, and computational modeling is the reverse-engineering and reproduction of Caenorhabditis elegans using computer simulation. The aim of our research was to develop the computational models and techniques for solving this problem while participating in the international open science OpenWorm Project. We have suggested models of a typical C. elegans neuron and a pharyngeal muscle cell, which were constructed and optimized using the NEURON simulation environment. The available experimental data about EGL-19 and EXP-2 ion channels allowed the model of a muscle to reproduce the action potential time profile correctly. Also, the model of a neuron reproduces quite accurately the mechanism of neural signal transmission based on passive propagation. We believe our models to be promising for better representing the specifics of various nervous and muscular cell classes when adding the corresponding ion channel models. Moreover, they can be used to construct the networks of such elements.

scholarly journals A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Weidong Feng ◽  
Yinan Li ◽  
Pauline Dao ◽  
Jihad Aburas ◽  
Priota Islam ◽  
...  
Keyword(s):  
Ion Channels ◽  
Motor Neurons ◽  
General Principle ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Neurotransmitter Receptors ◽  
Dual Function ◽  
C Elegans ◽  
Neuronal Identity ◽  
Transcriptional Switch

To become and remain functional, individual neuron types must select during development and maintain throughout life their distinct terminal identity features, such as expression of specific neurotransmitter receptors, ion channels and neuropeptides. Here, we report a molecular mechanism that enables cholinergic motor neurons (MNs) in the C. elegans ventral nerve cord to select and maintain their unique terminal identity. This mechanism relies on the dual function of the conserved terminal selector UNC-3 (Collier/Ebf). UNC-3 synergizes with LIN-39 (Scr/Dfd/Hox4-5) to directly co-activate multiple terminal identity traits specific to cholinergic MNs, but also antagonizes LIN-39’s ability to activate terminal features of alternative neuronal identities. Loss of unc-3 causes a switch in the transcriptional targets of LIN-39, thereby alternative, not cholinergic MN-specific, terminal features become activated and locomotion defects occur. The strategy of a terminal selector preventing a transcriptional switch may constitute a general principle for safeguarding neuronal identity throughout life.

scholarly journals A Novel and Functionally Diverse Class of Acetylcholine-gated Ion Channels

2021 ◽  
Author(s):  
Iris Hardege ◽  
Julia Morud ◽  
William R Schafer
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Diverse Group ◽  
Anion Channels ◽  
C Elegans ◽  
Cholinergic Synapses ◽  
Inhibitory Potential ◽  
Gated Ion Channels

Fast cholinergic neurotransmission is mediated by pentameric acetylcholine-gated ion channels; in particular, cationic nicotinic acetylcholine receptors play well-established roles in virtually all nervous systems. Acetylcholine-gated anion channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well-understood. Here we describe the functional properties of five previously-uncharacterized acetylcholine-gated anion channels from C. elegans, including four from a novel nematode specific subfamily known as the diverse group. In addition to their activation by acetylcholine, these diverse group channels are activated at physiological concentrations by other ligands; three, encoded by the lgc-40, lgc-57 and lgc-58 genes, are activated by choline, while lgc-39 encoded channels are activated by octopamine and tyramine. Intriguingly, these and other acetylcholine-gated anion channels show extensive co-expression with cation-selective nicotinic receptors, implying that many cholinergic synapses may have both excitatory and inhibitory potential. Thus, the evolutionary expansion of cholinergic ligand-gated ion channels may enable complex synaptic signalling in an anatomically compact nervous system.

scholarly journals Mimicking human riboflavin responsive neuromuscular disorders by silencing flad‐1 gene in C. elegans : Alteration of vitamin transport and cholinergic transmission

IUBMB Life ◽  
2021 ◽  
Author(s):  
Piero Leone ◽  
Maria Tolomeo ◽  
Elisabetta Piancone ◽  
Pier Giorgio Puzzovio ◽  
Carla De Giorgi ◽  
...  
Keyword(s):  
Neuromuscular Disorders ◽  
Cholinergic Transmission ◽  
C Elegans

scholarly journals Dopamine Negatively Modulates the NCA Ion Channels in C. elegans

2016 ◽  
Author(s):  
Irini Topalidou ◽  
Kirsten Cooper ◽  
Laura Pereira ◽  
Michael Ailion
Keyword(s):  
Ion Channels ◽  
Dopamine Receptor ◽  
G Protein ◽  
G Proteins ◽  
Function Analysis ◽  
Small Gtpase ◽  
Resting Membrane Potential ◽  
Membrane Excitability ◽  
C Elegans ◽  
Dopamine Signaling

AbstractThe NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels.Author summaryDopamine is a neurotransmitter that acts in the brain by binding seven transmembrane receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Neuronal G proteins often function by modulating ion channels that control membrane excitability. Here we identify a molecular cascade downstream of dopamine in the nematode C. elegans that involves activation of the dopamine receptor DOP-3, activation of the G protein GOA-1, and inactivation of the NCA-1 and NCA-2 ion channels. We also identify a G protein-coupled receptor kinase (GRK-2) that inactivates the dopamine receptor DOP-3, thus leading to inactivation of GOA-1 and activation of the NCA channels. Thus, this study connects dopamine signaling to activity of the NCA channels through G protein signaling pathways.

scholarly journals DEG/ENaC/ASIC channels vary in their sensitivity to anti-hypertensive and non-steroidal anti-inflammatory drugs

2020 ◽  
Author(s):  
S. Fechner ◽  
I. D’Alessandro ◽  
L. Wang ◽  
C. Tower ◽  
L. Tao ◽  
...  
Keyword(s):  
Ion Channels ◽  
Drug Sensitivity ◽  
Family Members ◽  
Extracellular Domain ◽  
Mechanical Stimuli ◽  
C Elegans ◽  
Acid Sensing Ion Channels ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Hypertensive Drug

AbstractThe degenerin channels, epithelial sodium channels, and acid-sensing ion channels (DEG/ENaC/ASICs) play important roles in sensing mechanical stimuli, regulating salt homeostasis, and responding to acidification in the nervous system. They have two transmembrane domains separated by a large extracellular domain and are believed to assemble as homomeric or heteromeric trimers. Based on studies of selected family members, these channels are assumed to form non-voltage gated and sodium-selective channels sensitive to the anti-hypertensive drug, amiloride. They are also emerging as a target of nonsteroidal anti-inflammatory drugs (NSAIDs).C. eleganshas more than two dozen genes encoding DEG/ENaC/ASIC subunits, providing an excellent opportunity to examine variations in drug sensitivity. Here, we analyze a subset of theC. elegansDEG/ENaC/ASIC proteins to test the hypothesis that individual family members vary not only in their ability to form homomeric channels, but also in their drug sensitivity. We selected fiveC. elegansDEG/ENaC/ASICs (DEGT-1, DEL-1, UNC-8, MEC-10 and MEC-4) that are co-expressed in mechanosensory neurons and expressed gain-of-function‘d’mutant isoforms inXenopus laevisoocytes. We found that only DEGT-1d, UNC-8d, and MEC-4d formed homomeric channels and that, unlike MEC-4d and UNC-8d, DEGT-1d channels were insensitive to amiloride and its analogs. As reported for rat ASIC1a, NSAIDs inhibit DEGT-1d and UNC-8d channels. Unexpectedly, MEC-4d was strongly potentiated by NSAIDs, an effect that was decreased by mutations in the putative NSAID binding site in the extracellular domain. Collectively, these findings reveal that not all DEG/ENaC/ASIC channels are amiloride-sensitive and that NSAIDs can both inhibit and potentiate these channels.SummaryAnimal physiology depends on degenerin, epithelial sodium, and acid-sensing ion channels (DEG/ENaC/ASICs). By measuring the sensitivity of threeC. elegansDEG/ENaC/ASICs to five amiloride analogs and five NSAIDs, we show that individual channels have distinct pharmacological footprints.

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