A calcium channel mutant mouse model of hypokalemic periodic paralysis

• DOI: 10.1172/jci66091
• Publication Date: 2012-11-26T13:00:17Z
• Authors: Fenfen Wu; Wentao Mi; Erick O. Hernánde...; Dennis K. Burns; Yu Fu; Hillery F. Gray; Arie F. Struyk; Martin F. Schneider; Stephen C. Cannon
• Keywords: Hypokalemic periodic paralysis; Muscle weakness

Hypokalemic periodic paralysis (HypoPP) is a familial skeletal muscle disorder that presents with recurrent episodes of severe weakness lasting hours to days associated reduced serum potassium (K+). HypoPP genetically heterogeneous, missense mutations calcium channel (CaV1.1) or sodium (NaV1.4) accounting for 60% and 20% cases, respectively. The mechanistic link between CaV1.1 the ictal loss excitability during an attack in unknown. To address this question, we developed mouse model targeted R528H mutation. Cav1.1 mice had phenotype which low K+ challenge produced paradoxical depolarization resting potential, excitability, weakness. A vacuolar myopathy dilated transverse tubules disruption triad junctions impaired Ca2+ release likely contributed mild permanent Fibers from small anomalous inward current at similar our observations NaV1.4 R669H model. This “gating pore current” may be common mechanism susceptibility arising S4 voltage sensor either channels.