Hypokalaemic periodic paralysis with a charge-retaining substitution in the voltage sensor.

ABSTRACT: Familial hypokalaemic periodic paralysis is a rare skeletal muscle disease caused by the dysregulation of sarcolemmal excitability. Hypokalaemic periodic paralysis is characterized by repeated episodes of paralytic attacks with hypokalaemia, and several variants in CACNA1S coding for Ca_V1.1 and SCN4A coding for Na_V1.4 have been established as causative mutations. Most of the mutations are substitutions to a non-charged residue, from the positively charged arginine (R) in transmembrane segment 4 (S4) of a voltage sensor in either Ca_V1.1 or Na_V1.4. Mutant channels have aberrant leak currents called 'gating pore currents', and the widely accepted consensus is that this current is the essential pathological mechanism that produces susce

SUBMITTER: Kubota T 

PROVIDER: S-EPMC7519726 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature