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https://hdl.handle.net/2440/119880
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Type: | Journal article |
Title: | Nav1.6 regulates excitability of mechanosensitive sensory neurons |
Author: | Israel, M.R. Tanaka, B.S. Castro Kraftchenko, J. Thongyoo, P. Robinson, S.D. Zhao, P. Deuis, J.R. Craik, D.J. Durek, T. Brierley, S.M. Waxman, S.G. Dib-Hajj, S.D. Vetter, I. |
Citation: | The Journal of Physiology, 2019; 597(14):1-18 |
Publisher: | Wiley |
Issue Date: | 2019 |
ISSN: | 0022-3751 1469-7793 |
Statement of Responsibility: | Mathilde R. Israel, Brian S. Tanaka, Joel Castro, Panumart Thongyoo, Samuel D. Robinson, Peng Zhao, Jennifer R. Deuis, David J. Craik, Thomas Durek, Stuart M. Brierley, Stephen G Waxman, Sulayman D. Dib-Hajj, Irina Vetter |
Abstract: | Peripheral sensory neurons express multiple voltage-gated sodium channels (NaV ) critical for the initiation and propagation of action potentials and transmission of sensory input. Three pore-forming sodium channel isoforms are primarily expressed in the peripheral nervous system (PNS): NaV 1.7, NaV 1.8 and NaV 1.9. These sodium channels have been implicated in painful and painless channelopathies and there has been intense interest in them as potential therapeutic targets in human pain. Emerging evidence suggests NaV 1.6 channels are an important isoform in pain sensing. This study aimed to assess, using pharmacological approaches, the function of NaV 1.6 channels in peripheral sensory neurons. The potent and NaV 1.6 selective β-scorpion toxin Cn2 was used to assess the effect of NaV 1.6 channel activation in the PNS. The multidisciplinary approach included Ca2+ imaging, whole-cell patch-clamp recordings, skin-nerve and gut-nerve preparations and in vivo behavioural assessment of pain. Cn2 facilitates NaV 1.6 early channel opening, and increased persistent and resurgent currents in large-diameter dorsal root ganglion (DRG) neurons. This promotes enhanced excitatory drive and tonic action potential firing in these neurons. In addition, NaV 1.6 channel activation in the skin and gut leads to increased response to mechanical stimuli. Finally, intra-plantar injection of Cn2 causes mechanical but not thermal allodynia. This study confirms selectivity of Cn2 on NaV 1.6 channels in sensory neurons. Activation of NaV 1.6 channels, in terminals of the skin and viscera, leads to profound changes in neuronal responses to mechanical stimuli. In conclusion, sensory neurons expressing NaV 1.6 are important for the transduction of mechanical information in sensory afferents innervating the skin and viscera. |
Keywords: | Skin colon dorsal root ganglia ion channels nociception pain patch clamp |
Rights: | © 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society |
DOI: | 10.1113/jp278148 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1139366 http://purl.org/au-research/grants/nhmrc/1126378 http://purl.org/au-research/grants/nhmrc/GNT1162503 http://purl.org/au-research/grants/arc/FL150100146 |
Published version: | http://dx.doi.org/10.1113/jp278148 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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