DEG/ENaC but Not TRP Channels Are the Major Mechanoelectrical Transduction Channels in a C. elegans Nociceptor

Geffeney, Shana L.; Cueva, Juan G.; Glauser, Dominique A.; Doll, Joseph C.; Lee, Tim Hau-Chen; Montoya, Misty M.; Karania, Snetu; Garakani, Arman; Pruitt, Beth L.; Goodman, Miriam B.

doi:10.1016/j.neuron.2011.06.038

Cited by 127 publications

(145 citation statements)

References 63 publications

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“…In four classes, including the touch receptor neurons (TRNs), such currents are sodium dependent and amiloride sensitive. Genetic dissection links these MeT currents to DEG/ENaC (degenerin/epithelial sodium channel) proteins in the TRNs (9-13) and a ciliated nociceptor (14)(15)(16). A transient receptor potential protein performs the role in a fifth class of mechanoreceptor that functions as a texture sensor (9,(17)(18)(19)(20).…”

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confidence: 99%

Tissue mechanics govern the rapidly adapting and symmetrical response to touch

Eastwood

Sanzeni

Petzold

et al. 2015

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

150

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Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities.

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confidence: 99%

Tissue mechanics govern the rapidly adapting and symmetrical response to touch

Eastwood

Sanzeni

Petzold

et al. 2015

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

150

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“…A recent study using the nematode model has shed some light on the topic (17). Geffeney et al (17) elegantly demonstrated that worms with mutations in a degenerin gene (DEG-1) or a TRP gene (TRPV) lack the integrated behavioral responses to stimulation. However, worms with the TRPV mutation have normal mechanoreceptor currents and potential, whereas DEG-1 mutant worms do not.…”

Section: Discussionmentioning

confidence: 99%

βENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells

Chung

Weissman

Farley

et al. 2013

American Journal of Physiology-Renal Physiology

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Chung WS, Weissman JL, Farley J, Drummond HA. ␤ENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells. Am J Physiol Renal Physiol 304: F1428 -F1437, 2013. First published April 3, 2013 doi:10.1152/ajprenal.00444.2012.-Myogenic constrictor responses in small renal arteries and afferent arterioles are suppressed in mice with reduced levels of ␤-epithelial Na ϩ channel (␤ENaC m/m ). The underlying mechanism is unclear. Decreased activity of voltage-gated calcium channels (VGCC) or mechanically gated ion channels and increased activity of large conductance calcium-activated potassium (BK) channels are a few possible mechanisms. The purpose of this study was to determine if VGCC, BK, or mechanically gated ion channel activity was altered in renal vascular smooth muscle cell (VSMC) from ␤ENaC m/m mice. To address this, we used whole cell patch-clamp electrophysiological approaches in freshly isolated renal VSMCs. Compared with ␤ENaC ϩ/ϩ controls, the current-voltage relationships for VGCC and BK activity are similar in ␤ENaC m/m mice. These findings suggest neither VGCC nor BK channel dysfunction accounts for reduced myogenic constriction in ␤ENaC m/m mice. We then examined mechanically gated currents using a novel in vitro assay where VSMCs are mechanically activated by stretching an underlying elastomer. We found the mechanically gated currents, predominantly carried by Na ϩ , are observed with less frequency (87 vs. 43%) and have smaller magnitude (Ϫ54.1 Ϯ 12.5 vs. Ϫ20.9 Ϯ 4.9 pA) in renal VSMCs from ␤ENaC m/m mice. Residual currents are expected in this model since VSMC ␤ENaC expression is reduced by 50%. These findings suggest ␤ENaC is required for normal mechanically gated currents in renal VSMCs and their disruption may account for the reduced myogenic constriction in the ␤ENaC m/m model. Our findings are consistent with the role of ␤ENaC as a VSMC mechanosensor and function of evolutionarily related nematode degenerin proteins.epithelial Na ϩ channel; ion channel; degenerin; myogenic constriction THE MYOGENIC RESPONSE IS AN inherent property of small arteries and arterioles in certain organs, including the kidney. The myogenic response is characterized by vasoconstriction following an increase in intraluminal pressure and vasodilation following a decrease in intraluminal pressure. Myogenic constriction is a physiologically relevant response. In the kidney, it is an important mechanism of renal autoregulation, critical for maintaining normal renal blood flow and glomerular filtration rate with changes in perfusion pressure. Recent studies also suggest myogenic constriction plays an important role in protecting against pressure-related renal injury by preventing transmission of systemic pressure swings to delicate renal microvasculature (28,29,42).There are at least three ion channels that play important roles in the myogenic response; mechanically gated ion channels, voltage-gated calcium channels (VGCC), and large conductance calcium activated potassium (BK) channels...

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“…The molecular mechanisms underlying proprioceptive transduction have just begun to be elucidated. Among mechanosensitive ion channel candidates such as certain members of the transient receptor potential (TRP) channels (12)(13)(14), degenerin/epithelial sodium channels (DEG/ENaC) (15)(16)(17), Piezo (18)(19)(20), transmembrane channel-like (TMC) (21), K2P (22)(23)(24), and MscL (large-conductance mechanosensitive channel) (24,25), TRPN and DEG/ENaC ion channels have been proposed to be mechanosensitive ion channels involved in proprioception in nematodes (26,27), fruit flies (6,9,10) and zebrafish (28). Recently, it was reported that Piezo2 is essential for the mechanosensitivity of mammalian proprioceptors (29).…”

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confidence: 99%

Transmembrane channel-like ( tmc ) gene regulates Drosophila larval locomotion

Guo¹,

Wang²,

Zhang³

et al. 2016

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

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Drosophila larval locomotion, which entails rhythmic body contractions, is controlled by sensory feedback from proprioceptors. The molecular mechanisms mediating this feedback are little understood. By using genetic knock-in and immunostaining, we found that the Drosophila melanogaster transmembrane channel-like (tmc) gene is expressed in the larval class I and class II dendritic arborization (da) neurons and bipolar dendrite (bd) neurons, both of which are known to provide sensory feedback for larval locomotion. Larvae with knockdown or loss of tmc function displayed reduced crawling speeds, increased head cast frequencies, and enhanced backward locomotion. Expressing Drosophila TMC or mammalian TMC1 and/or TMC2 in the tmc-positive neurons rescued these mutant phenotypes. Bending of the larval body activated the tmc-positive neurons, and in tmc mutants this bending response was impaired. This implicates TMC's roles in Drosophila proprioception and the sensory control of larval locomotion. It also provides evidence for a functional conservation between Drosophila and mammalian TMCs.proprioception | locomotion | mechanosensation

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DEG/ENaC but Not TRP Channels Are the Major Mechanoelectrical Transduction Channels in a C. elegans Nociceptor

Cited by 127 publications

References 63 publications

Tissue mechanics govern the rapidly adapting and symmetrical response to touch

Tissue mechanics govern the rapidly adapting and symmetrical response to touch

βENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells

Transmembrane channel-like ( tmc ) gene regulates Drosophila larval locomotion

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