Figure 5. NAC treatment prevents the decline in cytosolic Ca²⁺ concentration during trains of 60 Hz stimulation in FDB fibers from CASQ1-null mice and improves grip strength in CASQ1-null mice.

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 (t_f)) 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.