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Papers of the Week

Papers: 11 May 2019 - 17 May 2019

Animal Studies, Pharmacology/Drug Development

2019 Jul

J Physiol



Na 1.6 regulates excitability of mechanosensitive sensory neurons.


Israel MR, Tanaka BS, Castro J, Thongyoo P, Robinson SD, Zhao P, Deuis JR, Craik DJ, Durek T, Brierley SM, Waxman SG, Dib-Hajj SD, Vetter I
J Physiol. 2019 Jul; 597(14):3751-3768.
PMID: 31087362.


Peripheral sensory neurons express multiple voltage-gated sodium channels (Na ) 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): Na 1.7, Na 1.8 and Na 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 Na 1.6 channels are an important isoform in pain sensing. This study aimed to assess, using pharmacological approaches, the function of Na 1.6 channels in peripheral sensory neurons. The potent and Na 1.6 selective β-scorpion toxin Cn2 was used to assess the effect of Na 1.6 channel activation in the PNS. The multidisciplinary approach included; Ca imaging, whole-cell patch-clamp recordings, skin- and gut-nerve preparations and in vivo behavioural assessment of pain behaviours. Cn2 facilitates Na 1.6 early channel opening, increased persistent and resurgent currents in large diameter DRG neurons. This promotes enhanced excitatory drive and tonic action potential firing in these neurons. In addition, Na 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 Na 1.6 channels in sensory neurons. Activation of Na 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 Na 1.6 are important for the transduction of mechanical information in sensory afferents innervating the skin and viscera. This article is protected by copyright. All rights reserved.