Papers of the Week

The voltage-gated sodium channel Nav1.7 is essential for adequate perception of painful stimuli. Mutations in the encoding gene, SCN9A, cause various pain syndromes in human patients. The hNav1.7/A1632E mutant causes symptoms of erythromelalgia and paroxysmal extreme pain disorder (PEPD), and its main gating change is a strongly enhanced persistent current. On the basis of recently published 3D structures of voltage-gated sodium channels, we investigated how the inactivation particle binds to the channel, how this mechanism is interfered with by the hNav1.7/A1632E mutation, and how dimerization modifies function of the pain-linked mutation.