Fig. 5

Activation of SERCA1a and inhibition of RyR1 leak attenuates ECC-induced force loss of mdx muscle. a Eccentric force loss of isolated mdx EDL muscle incubated with small molecule SERCA1a activators (DS-11966966 and CDN1163) at their optimal concentration (^*DS-11966966 different from vehicle and ^#CDN1163 different from vehicle); b ryanodine receptor (RyR1) leak inhibitors (Chloroxine and Myricetin) at their optimal concentration (^*Chloroxine different from vehicle, ^#Myricetin different from vehicle); c a combination of CDN1163 and Myricetin, a combination of CDN1163 + Myricetin + 20 mM N-acetyl cysteine (NAC) (^*different from vehicle); and (d) isometric force as percent of initial immediately following the 10th eccentric contraction with and without all SERCA1a and RyR1 small-molecule modulators. e Maximal rates of tetanic contraction and f maximal rates of tetanic relaxation as a percent of initial of mdx EDL muscle with or without 20 mM N-acetyl cysteine (NAC). ^*Different from mdx. All ECC protocols were completed with a 5% length change. ^*Different from vehicle, ^#different from vehicle and DS-11966966, and ^$different from vehicle, DS-11966966, Chloroxine, CDN1163, and Myricetin. Data are mean ± S.E.M with significance set at p < 0.05. N = 5–12/compound or combination of compounds