A sodium channel gene SCN9A polymorphism that increases nociceptor excitability

摘要: Sodium channel Na(V)1.7, encoded by the SCN9A gene, is preferentially expressed in nociceptive primary sensory neurons, where it amplifies small depolarizations. In studies on a family with inherited erythromelalgia associated Na(V)1.7 gain-of-function mutation A863P, we identified nonsynonymous single-nucleotide polymorphism within affected proband and several unaffected members; this (c. 3448C&T, Single Nucleotide Polymorphisms database rs6746030, which produces amino acid substitution R1150W human [hNa(V)1.7]) present 1.1 to 12.7% of control chromosomes, depending ethnicity. study, examined effect function hNa(V)1.7 channel, firing dorsal root ganglion (DRG) neurons normally expressed. We show that depolarizes activation (7.9-11mV different assays). Current-clamp analysis shows 1150W allele (6mV) resting membrane potential increases ( approximately 2-fold) frequency response depolarization DRG present. Our results suggest polymorphisms may influence susceptibility pain.