Pre-incubation with simvastatin decreases the 4-CmC-modulated cytosolic Ca2+response in isolated FDB fibers from YS compared to WT mice. Represented as the change (Δ) from baseline to peak values, (A) shows that upon exposure to 1 mM 4-CmC those YS fibers incubated for 3 minutes in 500 μM simvastatin (YS-Sim) release significantly less Ca2+ from the SR than YS fibers receiving vehicle-only (YS-Veh) incubation (P <0.01) and from YS fibers incubated in 1 mM AICAR followed by 500 μM simvastatin (YS-Sim + AICAR) (P <0.05). Numbers represent total fibers used per group from a minimum of three mice. (B) YS and (C) WT show representative Mag-fluo-4 fluorescence tracings in single fibers exposed to either simvastatin or vehicle. Arrows indicate the time point at which 4-CmC was applied to the fibers. AICAR, 5-aminoimidazole-4-carboxamide ribonucleoside; 4-CmC, 4-chloro-m-cresol; Ca2+, calcium; FDB, flexor digitorum brevis; SR, sarcoplasmic reticulum; WT, wild type; YS, Y524S.