Fig. 4.

Stabilization of RyR1 channels slows muscle fatigue and reduces damage. (A) Representative trace of fluorescence (ΔF/F0) from a vehicle-treated FDB fiber loaded with fluo-4 normalized to the peak during repeated 300-ms, 120-Hz field-stimulated tetani at 0.5 Hz. Isolated cells were continuously perfused with Hepes-buffered Tyrodes solution at room temperature. (B) Representative (ΔF/F0) Ca²⁺ tetanic trace from an S107-treated FDB fiber. (C) Mean peak tetanic Ca²⁺ normalized to the peak during fatiguing stimulation (n = 6, vehicle; n = 9, S107). *, P < 0.05 unpaired t test. (D) Representative traces of RyR1 channel activity at 90 nM [Ca²⁺]_cis from sedentary mice (sed, Left), mice exercised and treated with vehicle (Ex + veh, Center), and mice exercised and treated with S107 (Ex + S107, Right). Single channel openings are plotted as upward deflections; the open and closed (c) states of the channel are indicated by horizontal bars at the beginning of the traces. Channel open probability (P_o), mean open time (T_o) and frequency of openings (F_o) are shown above each group of traces and represent average values from all experiments. (E) Average values of P_o (Left), T_o (Center), and F_o (Right) of RyR1 from sedentary mice (sed, n = 9) and exercised mice treated either with vehicle (Ex + veh, n = 9) or S107 (Ex + S107, n = 12). (F) Calpain activity levels in EDL homogenates. (G) Plasma creatine kinase (CPK) activity levels in sedentary and exercised mice with, and without, calstabin1 rebinding with S107. Data are presented as mean ± SEM; **, P < 0.01 compared with sed; #, P < 0.01 compared with Ex + veh.