Molecular Medicine Abnormal Termination of Ca Release Is a Common Defect of RyR2 Mutations Associated With Cardiomyopathies

Methods and Results: The 35-residue exon-3 region of RyR2 is associated with dilated cardiomyopathy. Single-cell luminal Ca imaging revealed that the deletion of the first 305 NH2-terminal residues encompassing exon-3 or the deletion of exon-3 itself markedly reduced the luminal Ca threshold at which Ca release terminates and increased the fractional Ca release. Single-cell cytosolic Ca imaging also showed that both RyR2 deletions enhanced the amplitude of store overload-induced Ca transients in HEK293 cells or HL-1