beta 3, a novel auxiliary subunit for the voltage-gated sodium channel, isexpressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain

Adult dorsal root ganglia (DRG) have been shown to express a wide range of voltage-gated sodium channel alpha -subunits. However, of the auxiliary sub units, beta1 is expressed preferentially in only large- and medium-diameter neurons of the DRG while beta2 is absent in all DRG cells. In view of this , we have compared the distribution of beta1 in rat DRG and spinal cord wit h a novel, recently cloned beta1-like subunit, beta3. In situ hybridization studies demonstrated high levels of beta3 mRNA in small-diameter c-fibres, while beta1 mRNA was virtually absent in these cell types but was expresse d in 100% of large-diameter neurons. In the spinal cord, beta3 transcript w as present specifically in layers I/II (substantia gelatinosa) and layer X, while beta1 mRNA was expressed in all laminae throughout the grey matter. Since the pattern of beta3 expression in DRG appears to correlate with the TTX-resistant voltage-gated sodium channel subunit PN3, we co-expressed the two subunits in Xenopus oocytes. In this system, beta3 caused a 5-mV hyper polarizing shift in the threshold of activation of PN3, and a threefold inc rease in the peak current amplitude when compared with PN3 expressed alone. On the basis of these results, we examined the expression of beta -subunit s in the chronic constriction injury model of neuropathic pain. Results rev ealed a significant increase in beta3 mRNA expression in small-diameter sen sory neurons of the ipsilateral DRG. These results show that beta3 is the d ominant auxiliary sodium channel subunit in small-diameter neurons of the r at DRG and that it is significantly upregulated in a model of neuropathic p ain.