Anomalous enhancement of resurgent Na⁺ currents at high temperatures by SCN9A mutations underlies the episodic heat-enhanced pain in inherited erythromelalgia.

ABSTRACT: Inherited erythromelalgia (IEM), caused by mutations in Na_v1.7 channel is characterized by episodic neuropathic pain triggered especially by warm temperature. However, the mechanism underlying the temperature-dependent episodic attacks of IEM remains elusive. We investigated the electrophysiological effect of temperature changes on Na_v1.7 channels with three different mutations, p.I136V, p. I848T, and p.V1316A, both in vitro and in vivo. In vitro biophysical studies of the mutant channels show consistent temperature-dependent enhancement of the relative resurgent currents if normalized to the transient currents, as well as temperature-dependent changes in the time to peak and the kinetics of decay of the resurgent currents, but no congruent temperature-dependent chang

SUBMITTER: Huang CW 

PROVIDER: S-EPMC6706385 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature