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After transection of their axons within the sciatic nerve, DRG neurons become hyperexcitable. Recent studies have demonstrated the emergence of a rapidly repriming tetrodotoxin (TTX)-sensitive sodium current that may account for this hyperexcitability in axotomized small (<27 microm diam) DRG neurons, but its molecular basis has remained unexplained. It has(More)
Antisera directed against unique peptide regions from each of the human brain voltage-gated sodium channel alpha subunits were generated. In immunoblots these were found to be highly specific for the corresponding recombinant polypeptides and to recognise the native holoprotein in human brain membrane preparations. These antisera were used to perform a(More)
The distribution of mRNAs encoding voltage-gated sodium channel alpha subunits (I, II, III, and VI) and beta subunits (beta1 and beta2) was studied in selected regions of the human brain by Northern blot and in situ hybridisation experiments. Northern blot analysis showed that all regions studied exhibited heterogenous expression of sodium channel(More)
Mutations of amino acid residues in the inner two-thirds of the S6 segment in domain III of the rat brain type IIA Na(+) channel (G1460A to I1473A) caused periodic positive and negative shifts in the voltage dependence of activation, consistent with an alpha-helix having one face on which mutations to alanine oppose activation. Mutations in the outer(More)
The voltage-gated sodium channel NaV1.8 (SNS, PN3) is thought to be a molecular correlate of the dorsal root ganglion (DRG) tetrodotoxin resistant (TTX-R) Na+ current. TTX-R/NaV1.8 is an attractive therapeutic drug target for inflammatory and neuropathic pain on the basis of its specific distribution in sensory neurones and its modulation by inflammatory(More)
Pichia pastoris is a methylotrophic yeast increasingly important in the production of therapeutic proteins. Expression vectors are based on the methanol-inducible AOX1 promoter and are integrated into the host chromosome. In most cases high copy number integration has been shown to be important for high-level expression. Since this occurs at low frequency(More)
Sea anemones are an important source of various biologically active peptides, and it is known that ATX-II from Anemonia sulcata slows sodium current inactivation. Using six different sodium channel genes (from Nav1.1 to Nav1.6), we investigated the differential selectivity of the toxins AFT-II (purified from Anthopleura fuscoviridis) and Bc-III (purified(More)
Voltage-gated sodium channels consist of a pore-forming alpha subunit and two auxiliary beta subunits. Excitable cells express multiple alpha subtypes, designated Na(v)1.1-Na(v)1.9, and three beta subunits, designated beta1, beta2 and beta3. Understanding how the different alpha subtypes, in combination with the various beta subunits, determine sodium(More)
We have cloned and expressed the full-length human Na(V)1.6 sodium channel cDNA. Northern analysis showed that the hNa(V)1.6 gene, like its rodent orthologues, is abundantly expressed in adult brain but not other tissues including heart and skeletal muscle. Within the adult brain, hNa(V)1.6 mRNA is widely expressed with particularly high levels in the(More)