The Voltage-Gated Anion Channels Encoded by<i>clh-3</i>Regulate Egg Laying in<i>C. elegans</i>by Modulating Motor Neuron Excitability

Branicky, Robyn; Mitsuya, Hiroaki; Strange, Kevin; Schafer, William R.

doi:10.1523/jneurosci.3112-13.2014

Cited by 33 publications

(43 citation statements)

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“…6C, D; F 1,13 = 41.93; P 6 0.001; N = 5 for treatment and control groups). Changes in the slope of the I-V curve were observed in VU-and BUM-treated neurons (P 6 0.05), possibly as a result of changes in currents mediated by either voltage-gated or Cl À -gated Cl À channels, which are sensitive to changes in intracellular Cl À levels (Wenning et al, 2001;Branicky et al, 2014). Together, these results indicate that differences in the N and P cell responses to GABA are a consequence of differences in Cl À homeostasis and that the drugs VU and BUM are capable of altering the Cl À homeostasis in these leech neurons in a manner consistent with their effects on vertebrate cells.…”

Section: Role Of CL à Exporters and Importersmentioning

confidence: 99%

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

et al. 2015

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GABA (γ-amino-butyric acid) -mediated signaling is normally associated with synaptic inhibition due to ionotropic GABA receptors that gate an inward Cl(-) current, hyperpolarizing the membrane potential. However, there are also situations where ionotropic GABA receptors trigger a Cl(-) efflux that results in depolarization. The well-characterized central nervous system of the medicinal leech was used to study the functional significance of opposing effects of GABA at the synaptic circuit level. Specifically, we focused on synapses made by the nociceptive N cell and the non-nociceptive P (pressure) cell that converge onto a common postsynaptic target. It is already known that GABA hyperpolarizes the P cell, but depolarizes the N cell and that inhibition of ionotropic GABA receptors by bicuculline (BIC) has opposing effects on the synapses made by these two inputs; enhancing P cell synaptic transmission, but depressing N cell synapses. The goal of the present study was to determine whether the opposing effects of GABA were due to differences in Cl(-) homeostasis between the two presynaptic neurons. VU 0240551 (VU), an inhibitor of the Cl(-) exporter K-Cl co-transporter isoform 2 (KCC2), attenuated GABA-mediated hyperpolarization of the non-nociceptive afferent while bumetanide (BUM), an inhibitor of the Cl(-) importer Na-K-Cl co-transporter isoform 1 (NKCC1), reduced GABA-mediated depolarization of the nociceptive neuron. VU treatment also enhanced P cell synaptic signaling, similar to the previously observed effects of BIC and consistent with the idea that GABA inhibits synaptic signaling at the presynaptic level. BUM treatment depressed N cell synapses, again similar to what is observed following BIC treatment and suggests that GABA has an excitatory effect on these synapses. The opposing effects of GABA could also be observed at the behavioral level with BIC and VU increasing responsiveness to non-nociceptive stimulation while BIC and BUM decreased responsiveness to nociceptive stimulation. These findings demonstrate that distinct synaptic inputs within a shared neural circuit can be differentially modulated by GABA in a functionally relevant manner.

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Section: Role Of CL à Exporters and Importersmentioning

confidence: 99%

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

et al. 2015

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“…The HSNs are critical regulators of egg-laying and link the egg-laying circuit to the rest of nervous system (54). Ca 2+ spikes in HSNs correlate with and likely trigger egg-laying events (55), because optogenetic stimulation of HSNs is sufficient to drive egg-laying (56)(57)(58). Does inhibition of egglaying by elevated CO 2 involve inhibition of HSN motor neurons?…”

Section: Resultsmentioning

confidence: 99%

Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

Fenk

Bono

2015

Proc. Natl. Acad. Sci. U.S.A.

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Carbon dioxide (CO 2 ) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO 2 , and previous work identified three neuron pairs called "BAG," "AFD," and "ASE" that respond to CO 2 stimuli. Using in vivo Ca 2+ imaging and behavioral analysis, we show that C. elegans can detect CO 2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO 2 with a rise in Ca 2+ . In contrast, glial sheath cells harboring the sensory endings of C. elegans' major chemosensory neurons exhibit strong and sustained decreases in Ca 2+ in response to high CO 2 . Some of these CO 2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO 2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO 2 . Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO 2 is elevated. CO 2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO 2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO 2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.neural circuit | behavioral choice | olfactory system | oviposition | glia M ost living matter creates temporal or spatial gradients of carbon dioxide (CO 2 ). Animals across phylogeny use such gradients to help detect food, conspecifics, or predators (1, 2). The ubiquity of CO 2 suggests that the ecologically relevant information it communicates will depend on the dynamics of the CO 2 stimulus and on context. CO 2 -responsive excitable cells have been identified in mammals (3), arthropods (4), and nematodes (5, 6). However, the number of CO 2 -responsive neurons that are functional in vivo, how they are embedded in neural circuits, and how they shape behavior is unclear.CO 2 crosses membranes readily and dissolves to generate CO 2 (aq), H + , and HCO 3 − . Many proteins whose activity is modified by CO 2 or its solvation products have been identified. pH changes can modulate G protein-coupled receptors (7), Ca 2+ -activated K + channels (8), inwardly rectifying K + channels (9), two pore domain K + channels (10), transient receptor potential (TRP) channels (11, 12), acid-sensing ion channels (ASICs) (13,14), and Pyk2 and ErbB1/2 kinases (15). HCO 3 − modulates soluble adenylate cyclase (16) and transmembrane guanylate cyclases (17); and CO 2 (aq) has been proposed to regulate transmembrane guanylate cyclases (18) and connexin 26 (19) directly. Cells expressing any of these proteins potentially could transduce changes in CO 2 /H + , raising the question: Do animals use a few specific sensory channe...

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“…Previous studies have shown that ClC-2 is also regulated by hormones (89–91), drugs (92–100), proteins (101–107), kinases (108–114), transcription factors (115,116), inhibitors (117–120), scorpion venom (121), α1-adrenoceptor (122), Plasmodium berghei (123), adenosine triphosphate (124,125), ClH 3 (40,126–137), permeant anions (138,139), membrane cholesterol (140) and the tyrosine endocytosis motif (141). …”

Section: Functional Properties Of Clc-2mentioning

confidence: 99%

Research and progress on ClC-2

Wang

Kong

et al. 2017

Molecular Medicine Reports

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Chloride channel 2 (ClC-2) is one of the nine mammalian members of the ClC family. The present review discusses the molecular properties of ClC-2, including CLCN2, ClC-2 promoter and the structural properties of ClC-2 protein; physiological properties; functional properties, including the regulation of cell volume. The effects of ClC-2 on the digestive, respiratory, circulatory, nervous and optical systems are also discussed, in addition to the mechanisms involved in the regulation of ClC-2. The review then discusses the diseases associated with ClC-2, including degeneration of the retina, Sjögren's syndrome, age-related cataracts, degeneration of the testes, azoospermia, lung cancer, constipation, repair of impaired intestinal mucosa barrier, leukemia, cystic fibrosis, leukoencephalopathy, epilepsy and diabetes mellitus. It was concluded that future investigations of ClC-2 are likely to be focused on developing specific drugs, activators and inhibitors regulating the expression of ClC-2 to treat diseases associated with ClC-2. The determination of CLCN2 is required to prevent and treat several diseases associated with ClC-2.

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The Voltage-Gated Anion Channels Encoded byclh-3Regulate Egg Laying inC. elegansby Modulating Motor Neuron Excitability

Cited by 33 publications

References 43 publications

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

Research and progress on ClC-2

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The Voltage-Gated Anion Channels Encoded byclh-3Regulate Egg Laying inC. elegansby Modulating Motor Neuron Excitability

Cited by 33 publications

References 43 publications

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

Environmental CO 2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

Research and progress on ClC-2

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Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity