Hyperactivation of L-type voltage-gated Ca2+ channels in <i>C. elegans</i> striated muscle can result from point mutations in the IS6 or the IIIS4 segment of the α1 subunit.

Lainé, Viviane; Ségor, Jean Rony; Zhan, Hong; Bessereau, Jean-Louis; Jospin, Maëlle

doi:10.1242/jeb.106732

Cited by 26 publications

(32 citation statements)

References 77 publications

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“…Numerous alleles of egl-19 have been isolated, and some of them characterized and classified as reduction- or gain-of-function (r.o.f., g.o.f.) mutants, following different assays (in some cases by electrophysiology), based on EGL-19’s roles in development, pharynx, locomotion and egg-laying muscles 22 39 40 41 42 43 44 . We determined pump durations for a range of these mutants: Alleles ad695 , n582ad952 , ad995 , ad1015 , and n2368 showed increased pump duration ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Arrhythmogenic effects of mutated L-type Ca2+-channels on an optogenetically paced muscular pump in Caenorhabditis elegans

Schüler

Fischer

Shaltiel

et al. 2015

Sci Rep

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Cardiac arrhythmias are often associated with mutations in ion channels or other proteins. To enable drug development for distinct arrhythmias, model systems are required that allow implementing patient-specific mutations. We assessed a muscular pump in Caenorhabditis elegans. The pharynx utilizes homologues of most of the ion channels, pumps and transporters defining human cardiac physiology. To yield precise rhythmicity, we optically paced the pharynx using channelrhodopsin-2. We assessed pharynx pumping by extracellular recordings (electropharyngeograms—EPGs), and by a novel video-microscopy based method we developed, which allows analyzing multiple animals simultaneously. Mutations in the L-type VGCC (voltage-gated Ca2+-channel) EGL-19 caused prolonged pump duration, as found for analogous mutations in the Cav1.2 channel, associated with long QT syndrome. egl-19 mutations affected ability to pump at high frequency and induced arrhythmicity. The pharyngeal neurons did not influence these effects. We tested whether drugs could ameliorate arrhythmia in the optogenetically paced pharynx. The dihydropyridine analog Nemadipine A prolonged pump duration in wild type, and reduced or prolonged pump duration of distinct egl-19 alleles, thus indicating allele-specific effects. In sum, our model may allow screening of drug candidates affecting specific VGCCs mutations, and permit to better understand the effects of distinct mutations on a macroscopic level.

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Section: Resultsmentioning

confidence: 99%

Arrhythmogenic effects of mutated L-type Ca2+-channels on an optogenetically paced muscular pump in Caenorhabditis elegans

Schüler

Fischer

Shaltiel

et al. 2015

Sci Rep

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“…We predicted that either the removal of the Kr currents or a left shift of the activation voltage of EGL-19 would eliminate the delay to the first spike. Indeed, egl-19(ad695), a gain of function mutant in which the EGL-19 I-V curve is shifted by 6 mV toward negative potentials (Lainé et al, 2014), eliminated the delay to the first spike in almost all AWA recordings ( Figures 5E and 5F). This effect supports the identification of EGL-19 as a molecular mediator of the AWA action potential upstroke.…”

Section: Modeling Awa Action Potentials Based On Known and Predicted mentioning

confidence: 97%

C. elegans AWA Olfactory Neurons Fire Calcium-Mediated All-or-None Action Potentials

Liu

Kidd

Dobosiewicz

et al. 2018

Cell

110

133

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Neurons in Caenorhabditis elegans and other nematodes have been thought to lack classical action potentials. Unexpectedly, we observe membrane potential spikes with defining characteristics of action potentials in C. elegans AWA olfactory neurons recorded under current-clamp conditions. Ion substitution experiments, mutant analysis, pharmacology, and modeling indicate that AWA fires calcium spikes, which are initiated by EGL-19 voltage-gated CaV1 calcium channels and terminated by SHK-1 Shaker-type potassium channels. AWA action potentials result in characteristic signals in calcium imaging experiments. These calcium signals are also observed when intact animals are exposed to odors, suggesting that natural odor stimuli induce AWA spiking. The stimuli that elicit action potentials match AWA's specialized function in climbing odor gradients. Our results provide evidence that C. elegans neurons can encode information through regenerative all-or-none action potentials, expand the computational repertoire of its nervous system, and inform future modeling of its neural coding and network dynamics.

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“…Both cGMP and calcium levels increase in URX as a result of oxygen sensation. To determine if calcium alone is sufficient for dendritic branch growth, we took advantage of a gain-of-function allele of egl-19 , the sole L-type voltage-gated calcium channel in C. elegans [36]. The EGL-19 calcium channel is gated after depolarization of the URX neuron by CNG-1 and TAX-4 channels (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

Long-term activity drives dendritic branch elaboration of a C. elegans sensory neuron

Cohn

Cebul

Valperga

et al. 2019

Preprint

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23Neuronal activity often leads to alterations in gene expression and cellular architecture. 24 The nematode Caenorhabditis elegans, owing to its compact translucent nervous 25 system, is a powerful system in which to study conserved aspects of the development 26 and plasticity of neuronal morphology. Here we focus on one sensory neuron in the 27 worm, termed URX, which senses oxygen and signals tonically proportional to 28 environmental oxygen. Previous studies have reported that URX has variable branched 29 endings at its dendritic sensory tip. By controlling oxygen levels and analyzing mutants, 30 we found that these branched endings grow over time as a consequence of neuronal 31 activity. Furthermore, we observed that the branches contain microtubules, but do not 32 appear to harbor the guanylyl cyclase GCY-35, a central component of the oxygen 33 sensory transduction pathway. Interestingly, we found that although URX dendritic tips 34 grow branches in response to long-term activity, the degree of branch elaboration does 35 not correlate with oxygen sensitivity at the cellular or the behavioral level. Given the 36 strengths of C. elegans as a model organism, URX may serve as a potent system for 37 uncovering genes and mechanisms involved in activity-dependent morphological 38 changes in neurons. 46 prolonged input or activity. These activity-dependent changes in neuron shape allow 47 animals to interact more adeptly with their environment. For instance, the growth and 48 pruning of specific synapses as well as axon and dendritic branches allow neural 49 circuits to alter synaptic weighting during forms of learning and homeostatic plasticity [1, 50 2]. Interneurons also adjust the number and shape of their minute dendritic spines to 51 filter input differently in neuronal networks [3][4][5]. In the sensory system, photoreceptor 52 outer segment length has been shown to change in response to different light levels [6]. 53 Thus, although the gross structure of the adult nervous system often remains static, 54 many neurons change shape at subtle spatial and temporal scales. 55The transparency, genetic tractability, and compact nervous system of the 56 nematode C. elegans make the worm an excellent system to study genes that underlie 57 how neurons achieve and adjust their shape. Many aspects of neuronal morphology 58 have been examined in C. elegans, such as axonal and dendritic establishment [7, 8], 59 dendritic tiling [9], synapse specification [10], and sensory cilia morphogenesis and 60 maintenance [11, 12]. The worm has also been used to study how neurons alter their 61 shape in response to changes in environment, such as the reshaping of the ciliated 62 chemosensory neuron AWB by sensory activity [13], and the restructuring of sensory 63 neuronal endings in an alternative developmental larval stage termed dauer, which is 64 induced by certain environmental conditions [14][15][16]. Furthermore, many of the genes for the development and maintenance of sensory cilia in C. elegans have 66 cons...

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Hyperactivation of L-type voltage-gated Ca2+ channels in C. elegans striated muscle can result from point mutations in the IS6 or the IIIS4 segment of the α1 subunit.

Cited by 26 publications

References 77 publications

Arrhythmogenic effects of mutated L-type Ca2+-channels on an optogenetically paced muscular pump in Caenorhabditis elegans

Arrhythmogenic effects of mutated L-type Ca2+-channels on an optogenetically paced muscular pump in Caenorhabditis elegans

C. elegans AWA Olfactory Neurons Fire Calcium-Mediated All-or-None Action Potentials

Long-term activity drives dendritic branch elaboration of a C. elegans sensory neuron

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