Fig. 3.

Pharmacologic prevention of calstabin1 depletion from the RyR1 complex improves in vivo exercise capacity. (A) Time to failure during treadmill assays on indicated days of a 28-day treatment trial with S107. (B) Force–frequency curves of EDL muscle isolated immediately after the 21st day of exercise and isometrically stimulated in an oxygenated muscle bath. Forces (cN) are normalized to muscle cross-sectional area. (C) RyR1 immunoprecipitated from EDL and immunoblotted for RyR, RyR1-pS2844, Cys-NO, PDE4D3, and calstabin1. Data are presented as mean ± SEM; †, P < 0.05, Wilcoxon rank-sum test WT + S107 vs. WT + vehicle (veh); *, P < 0.05, unpaired t test. ex, exercise.