A–D) Representative fura-2 fluorescence ratio (F340/F380) traces obtained during sustained high frequency electrical stimulation (60 Hz, 2 seconds) in single FDB fibers from untreated WT (A), NAC-treated WT (B), untreated CASQ1-null (C), and NAC-treated CASQ1-null mice (D). The pronounced decline during 60 Hz stimulation in fibers from CASQ1-null mice is prevented by NAC treatment. E) Average (+/− SEM) fractional fura-2 ratio signal, calculated as the ratio between fura-2 ratio at the end of the stimulation (F (tf)) with that recorded at the start of the stimulation (F (t0)), during sustained 60 Hz stimulation in FDB fibers from untreated WT, NAC-treated WT, untreated CASQ1-null, and NAC-treated CASQ1-null mice (*p<0.01; n = number of fibers). NAC significantly reduces Ca2+ transient decline in FDB fibers from both WT and CASQ1-null mice. F) Time-course of grip strength from 2 (beginning of treatment) to 4 months (end of treatment) of age in untreated WT, NAC-treated WT, untreated CASQ1-null, and NAC-treated CASQ1-null mice. Grip strength was significantly (*p<0.01, n = number of mice) increased in NAC-treated CASQ1-null mice compared to untreated CASQ1-null mice, though still significantly reduced compared to that of untreated and NAC-treated WT mice. No significant differences were detected between untreated and NAC-treated WT mice. G) Bar graph showing the percent change in grip strength from 2 to 4 months of age in all four groups. Data are given as mean ± SEM. Abbreviations: CASQ1-null, Calsequestrin-1 knockout; FDB, flexor digitorum brevis; NAC, N-acetylcysteine; WT, wild type.