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Papers of the Week


Papers: 11 Jul 2020 - 17 Jul 2020


Pharmacology/Drug Development


2020 Jul 14


Br J Pharmacol

Editor's Pick

Uncoupling sodium channel dimers rescues the phenotype of a pain-linked Nav1.7 mutation.

Authors

Rühlmann AH, Körner J, Hausmann R, Bebrivenski N, Neuhof C, Detro-Dassen S, Hautvast P, Benasolo CA, Meents J, Machtens J-P, Schmalzing G, Lampert A
Br J Pharmacol. 2020 Jul 14.
PMID: 32663327.

Abstract

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.