Structural basis for gating pore current in periodic paralysis.

ABSTRACT: Potassium-sensitive hypokalaemic and normokalaemic periodic paralysis are inherited skeletal muscle diseases characterized by episodes of flaccid muscle weakness^1,2. They are caused by single mutations in positively charged residues ('gating charges') in the S4 transmembrane segment of the voltage sensor of the voltage-gated sodium channel Na_v1.4 or the calcium channel Ca_v1.1^1,2. Mutations of the outermost gating charges (R1 and R2) cause hypokalaemic periodic paralysis^1,2 by creating a pathogenic gating pore in the voltage sensor through which cations leak in the resting state^3,4. Mutations of the third gating charge (R3) cause normokalaemic periodic paralysis ⁵ owing to cation leak in both activated and inactiva

SUBMITTER: Jiang D 

PROVIDER: S-EPMC6708612 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature