Elevated resting H+ current in the R1239H type 1 hypokalaemic periodic paralysis mutated Ca2+ channel

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12603-list-0001">Missense mutations in the gene encoding the α1 subunit of the skeletal muscle voltage‐gated Ca²⁺ channel induce type 1 hypokalaemic periodic paralysis, a poorly understood neuromuscular disease characterized by episodic attacks of paralysis associated with low serum K⁺.Acute expression of human wild‐type and R1239H HypoPP1 mutant α1 subunits in mature mouse muscles showed that R1239H fibres displayed Ca²⁺ currents of reduced amplitude and larger resting leak inward current increased by external acidification.External acidification also produced intracellular acidification at a higher rate in R1239H fibres and inhibited inward rectifier K⁺ currents.These data suggest that the R1239H mutation induces an elevated leak H⁺ current at rest flowing through a gating pore and could explain why paralytic attacks preferentially occur during the recovery period following muscle exercise.