Inherited pain sodium channel nav1.7 A1632T mutation causes erythromelalgia due to a shift of fast inactivation

Abstract

Background: Mutations in the sodium channel Nav1.7 cause the inherited pain syndromes IEM and PEPD. Results: The new IEM mutation A1632T impairs channel inactivation, whereas an IEM/PEPD crossover mutation (A1632E) at the same position additionally increases resurgent sodium currents. Conclusion: Reduced inactivation without increased resurgent currents induces symptoms of IEM. Significance: Resurgent currents are likely to determine whether a mutation leads to IEM or PEPD. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.