Effect of myopathy mutations in Cav1.1 on DICR activity. (A) Schematic drawing of the location of myopathy mutations (E100K, F275L, P742Q, and L1367V) in Cav1.1. Note that WT and mutant Cav1.1s also carry N617D Ca²⁺ non-conducting mutation. (B) Resting ER [Ca²⁺] in cells expressing WT and mutant Cav1.1. Data are means ± SD (n = 12, N = 3) and were analyzed by one-way ANOVA with Dunnett’s multiple comparisons test. (C) Typical results of R-CEPIA1er fluorescence in cells infected with 5 BV carrying WT (left), F275L (center), and P742Q (right) Cav1.1. High [K⁺] solution ranging from 5 to 61 mM (symbols shown in left) was applied at 30 s after starting (blue arrowheads). (D) [K⁺] dependence of R-CEPIA1er fluorescence (F/F₀) in WT (black), E100K (red), F275L (blue), P742Q (green), and L1367V (magenta) Cav1.1 cells. Data are means ± SD (n = 9, N = 3). (E and F) Fluorescence change by 61 mM [K⁺] (E) and EC₅₀ values for [K⁺] (F). Data are means ± SD (n = 9, N = 3) and were analyzed by one-way ANOVA with Dunnett’s multiple comparisons test. (G) Caffeine dependence of R-CEPIA1er fluorescence (F/F₀) in WT (black), E100K (red), F275L (blue), P742Q (green), and L1367V (magenta) Cav1.1 cells. Data are means ± SD (n = 9, N = 3). (H and I) Fluorescence change by 20 mM caffeine (H) and EC₅₀ values for caffeine (I). Data are means ± SD (n = 9, N = 3) and were analyzed by one-way ANOVA with Dunnett’s multiple comparisons test. n is the number of wells and N is the number of independent experiments.