(A) Representative Ca2+ transients recorded in Fura-2 loaded cardiomyocytes from WT, PLN Tg, DWORF Tg, and PLN/DWORF Tg mice. (B) Mean peak amplitude of pacing-induced Ca2+ transients and transient decay rates (tau) (C) in Fura-2 loaded cardiomyocytes from WT, PLN Tg, DWORF Tg, and PLN/DWORF Tg mice. Transient decay rates were measured by fitting a single exponential to the decay phase of the Ca2+ transient. (D) Representative fractional shortening tracings as measured by sarcomere length during cardiomyocyte contraction. (E) Mean fractional shortening data from mice with the indicated genotypes. Data are represented as mean ±SD for n = 3 animals with 10–12 recordings per animal. Statistical comparisons between groups were evaluated by Student’s t-test. p-value *p<0.05, **p<0.01, ***p<0.005 or ****p<0.001 vs. WT and ###p<0.005 or ####p<0.001 vs. PLN Tg. (F, G) Ca2+-dependent Ca2+-uptake assays were performed using total homogenates from hearts of WT, PLN Tg, DWORF Tg, and PLN/DWORF Tg mice to directly measure SERCA affinity for Ca2+ (KCa) and SERCA activity. Representative tracings (F) and average KCa values (G) from n = 4 hearts of each genotype are represented as bar graphs (±SD). P-value *p<0.05, **p<0.01 or ***p<0.005 vs. WT and ##p<0.01 vs. PLN Tg.