title: Sodium channels and mammalian sensory mechanotransduction.
abstract: BACKGROUND
  Members of the degenerin/epithelial (DEG/ENaC) sodium channel family are mechanosensors in C elegans, and Nav1.7 and Nav1.8 voltage-gated sodium channel knockout mice have major deficits in mechanosensation. β and γENaC sodium channel subunits are present with acid sensing ion channels (ASICs) in mammalian sensory neurons of the dorsal root ganglia (DRG). The extent to which epithelial or voltage-gated sodium channels are involved in transduction of mechanical stimuli is unclear.
  
  
  RESULTS
  Here we show that deleting β and γENaC sodium channels in sensory neurons does not result in mechanosensory behavioural deficits. We had shown previously that Nav1.7/Nav1.8 double knockout mice have major deficits in behavioural responses to noxious mechanical pressure. However, all classes of mechanically activated currents in DRG neurons are unaffected by deletion of the two sodium channels. In contrast, the ability of Nav1.7/Nav1.8 knockout DRG neurons to generate action potentials is compromised with 50% of the small diameter sensory neurons unable to respond to electrical stimulation in vitro.
  
  
  CONCLUSIONS
  Behavioural deficits in Nav1.7/Nav1.8 knockout mice reflects a failure of action potential propagation in a mechanosensitive set of sensory neurons rather than a loss of primary transduction currents. DEG/ENaC sodium channels are not mechanosensors in mouse sensory neurons.
authors.affiliation: Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK. Ramin.Raouf@kcl.ac.uk
authors.forename: Ramin
authors.initials: R
authors.lastname: Raouf
authors.forename: Francois
authors.initials: F
authors.lastname: Rugiero
authors.forename: Hannes
authors.initials: H
authors.lastname: Kiesewetter
authors.forename: Rachel
authors.initials: R
authors.lastname: Hatch
authors.forename: Edith
authors.initials: E
authors.lastname: Hummler
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Nassar
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; C503479:Scn9a protein, mouse; D015222:Sodium Channels