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Sodium channels and mammalian sensory mechanotransduction

DOI: 10.1186/1744-8069-8-21

Keywords: Mechanotransduction, Sodium channels, Pain, Nav1.7, Nav1.8, ENaCs

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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.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.The identity of the noxious mechanotransduction channels in sensory neurons remains elusive but increasing evidence, particularly from knockout mice, indicates that transduction of noxious stimuli are carried out by more than one channel [1]. Many candidates have been proposed, however none has fulfilled the requirements of a bona fide noxious mechanotransducer that is expressed in mechanosensitive neurons, is activated by high threshold mechanical stimulation, and can be modulated by inflammatory mediators [2]. The list of potential mechanotransducers include TRP channels, potassium channels (see [1] for review), and the novel channel family Fam38a and b (Piezo1 and 2) transmembrane proteins [3]Some invertebrate sodium channels of the ENaC/DEG superfamily are mechanosensors [4-6] but it is still unknown if any mammalian epithelial or voltage gated sodium channels participate in noxious mechanotransduction. Evidence from knockout mice suggests that ASICs are not involved in sensory transduction [7]. Epithelial Na+ channels (ENaC) are voltage-independent, Na+-selective ion channels composed of α, β and γ


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