Sodium channels and mammalian sensory mechanotransduction

TY - JOUR

T1 - Sodium channels and mammalian sensory mechanotransduction

AU - Raouf, Ramin

AU - Rugiero, Francois

AU - Kiesewetter, Hannes

AU - Hatch, Rachel

AU - Hummler, Edith

AU - Nassar, Mohammed A.

AU - Wang, Fan

AU - Wood, John N.

PY - 2012/3/26

Y1 - 2012/3/26

N2 - 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. beta and gamma ENaC 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 beta and gENaC 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.Conclusion: 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.

AB - 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. beta and gamma ENaC 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 beta and gENaC 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.Conclusion: 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.

KW - Nav1.8

KW - ENaCs

KW - LAMINAR SHEAR-STRESS

KW - DRG NEURONS

KW - MICE LACKING

KW - Pain

KW - Nav1.7

KW - EPITHELIAL NA+ CHANNELS

KW - NA(V)1.8

KW - TRANSDUCTION

KW - ION-CHANNEL

KW - Sodium channels

KW - TOUCH RECEPTOR NEURONS

KW - INFLAMMATORY PAIN

KW - Mechanotransduction

KW - MECHANOSENSITIVITY

U2 - 10.1186/1744-8069-8-21

DO - 10.1186/1744-8069-8-21

M3 - Article

SN - 1744-8069

VL - 8

JO - Molecular Pain

JF - Molecular Pain

M1 - 21

ER -