β-Arrestin 1 is required for enhanced EDL force frequency upon carvedilol-mediated βAR activation. (A) Tissue lysates from muscle, heart, spleen of βarr1flox mice and βarr1smKO mice subjected to measure β-arrestin 1 expression by immunoblotting using anti-β-arrestin 1 antibody (A1ct). Equal amounts of tissue lysates loaded were probed by immunoblotting using anti-GAPDH antibody. Force–frequency curves for EDL muscles from βarr1flox and βarr1smKO mice after 2 wk of carvedilol (1 mg/kg/day), metoprolol (10 mg/kg/day), and clenbuterol (1 mg/kg/day) compared to vehicle (10% DMSO, 300 mM ascorbic acid in saline solution) treatment. Absolute force relationship was presented in βarr1Flox mice (B) and βarr1smKO mice (C). Specific force normalized to CSA was presented inβarr1Fox (D) and βarr1smKO mice (E). Specific force normalized to muscle weight was presented in βarr1Flox mice (F) and βarr1smKO mice(G). Data represent the mean ± SEM for n independent EDL muscles as marked in the figure. Statistical significance versus vehicle-treated group was performed by using a two-way ANOVA with Sidak’s multiple comparison test. P value from vehicle vs. clenbuterol in blue, vehicle vs. carvedilol in red, and vehicle vs. metoprolol in green.