Kinetic Alterations in Resurgent Sodium Currents of Mutant Na_v1.4 Channel in Two Patients Affected by Paramyotonia Congenita.

ABSTRACT: Paramyotonia congenita (PMC) is a rare skeletal muscle disorder characterized by muscle stiffness upon repetitive exercise and cold exposure. PMC was reported to be caused by dominant mutations in the SCN4A gene encoding the α subunit of the Na_v1.4 channel. Recently, we identified two missense mutations of the SCN4A gene, p.V781I and p.A1737T, in two PMC families. To evaluate the changes in electrophysiological properties caused by the mutations, both mutant and wild-type (WT) SCN4A genes were expressed in CHO-K1 and HEK-293T cells. Then, whole-cell patch-clamp recording was employed to study the altered gating of mutant channels. The activation curve of transient current showed a hyperpolarizing shift in both mutant Na_v1.4 channels as compared to the WT channel, wher

SUBMITTER: Lee MJ 

PROVIDER: S-EPMC9031228 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature