Impaired Dynamic Sarcoplasmic Reticulum Ca Buffering in Autosomal Dominant CPVT2

Abstract

<i>CASQ2-K180R</i> causes CPVT2 via a heretofore unknown mechanism that differs from <i>CASQ2</i> variants associated with autosomal recessive CPVT2. Unlike autosomal recessive <i>CASQ2</i> variants, K180R impairs the dynamic buffering of Ca within the SR without affecting total SR Ca content or Casq2 protein levels. Our data provide insight into the molecular mechanism underlying autosomal dominant CPVT2.