Sodium channels and mammalian sensory mechanotransduction

Molecular Pain

John N Wood¹  Fan Wang²  Mohammed A Nassar³  Edith Hummler⁵  Rachel Hatch⁴  Hannes Kiesewetter⁴  Francois Rugiero⁴  Ramin Raouf⁶ 

[1] DMMBPS, Seoul National University, Seoul 151-742, Korea;Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA;Biomedical Science University of Sheffield, Sheffield S10 2TN, UK;Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK;Department of Pharmacology and Toxicology, University of Lausanne, Lausanne 1005, Switzerland;Pfizer KCL Pain Lab, Wolfson Centre for Age-Related Diseases, King's College London, London, UK

关键词: ENaCs;    Nav1.8;    Nav1.7;    Pain;    Sodium channels;    Mechanotransduction;   

Others  :  865491
DOI  :  10.1186/1744-8069-8-21

 received in 2011-10-21, accepted in 2012-03-26,  发布年份 2012

【 摘 要 】

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.

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.

【 授权许可】

   
2012 Raouf et al; licensee BioMed Central Ltd.

【 图 表 】

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