Figure 3.

β-sarcoglycan deficient muscle displays RyR1 dysfunction and defective SR Ca²⁺release that is restored by S107 treatment. (A-C) Representative RyR1 single channel current traces in samples from WT (A), Sgcb−/− (B), and Sgcb−/− S107 (C) treated mice. Channel activity was measured at 90 nmol/L (nM) free cytosolic [Ca²⁺]. Channel openings are shown as upward deflections; the closed (c -) state of the channel is indicated by horizontal bars in the beginning of each tracing. For each group, channel activity is illustrated by four different traces, each of 5 s length as indicated by dimension bars. The single channel open probability (Po), To (mean open time) and Tc (mean closed time) were calculated from a 2 min recording under 90 nmol/L free cytosolic [Ca²⁺] are shown above the upper trace. (D) Bar graph summarizing RyR1 single channel Po under 90 nmol/L free cytosolic [Ca²⁺] from WT (n = 4; white bar), Sgcb−/− (n = 3; black bar), and Sgcb−/− + S107 (n = 4; red bar) samples. Data presented as mean ± S.E.M; * P <0.05; ** P <0.01 (ANOVA). (E) Representative tetanic Ca²⁺ transients (normalized Fluo-4 fluorescence) in FDB muscle fibers from wild-type (WT), β-sarcoglycan-deficient control (Sgcb−/−), and S107-treated β-sarcoglycan-deficient (Sgcb−/− S107) mice. (F) Average Ca²⁺ transient amplitudes (±SEM, n = 6 (WT) n =20 (Sgcb−/−), n = 26 (Sgcb−/− S107) cells from three mice in each group, * P <0.05, ** P <0.01 (ANOVA)).