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. Author manuscript; available in PMC: 2010 Jul 27.
Published in final edited form as: Nat Med. 2009 Feb 8;15(3):325–330. doi: 10.1038/nm.1916

Figure 3. Preventing calstabin1 depletion from the RyR1 complex with S107 improves grip strength and reduces muscle damage.

Figure 3

(a) We determined forelimb grip strength in sedentary mice after two weeks of treatment with S107 administered via an osmotic pump as described in the methods. (mdx-S107, n = 14, black diamond), vehicle (mdx-vehicle, n = 14, grey triangle), WT (n = 9, open square) mice. Data are presented as a scatter plot of absolute grip strength (ponds) versus body weight (BW, g). Least square fit lines are overlaid. (b) Grip strength normalized to BW. *, P < 0.015, t-test with Bonferroni adjustment, mdx-S107 vs mdx-veh. (c) CK levels (#, P < 0.015 vs. WT; *, P < 0.015 mdx-S107 vs. mdx-veh; t-tests with Bonferroni adjustment). (d) EDL tissue calpain activity (#,P < 0.015 vs. WT; *, P < 0.015 mdx-S107 vs. mdx-veh; t-tests with Bonferroni adjustment). (e) RyR1 immunoprecipitated from hind limb EDL muscle immunoblotted for total RyR1, RyR1-pS2844, Cys-NO, PDE4D3 and calstabin1 bound to RyR1. (f) Quantification of (e) showing levels of indicated proteins normalized to the total amount of RyR1 (AU, arbitrary units). Data presented as mean ± S.E.M. (#, P < 0.015 for RyR1-Cys-NO, mdx vs. WT; *, P < 0.015, for calstabin1 binding to RyR1, mdx treated with S107 vs. mdx treated with vehicle). (g) Immunoblot for iNOS, eNOS, and nNOS in EDL whole muscle lysates. (h) Representative images of DAPI stained 10 μm TA sections from mice injected with 100 μl of 1% Evans Blue Dye intraperitoneally 24 hrs prior to sacrifice. S107 treatment was begun at 35 days of age and continued for 4 wks via osmotic pump. (i) Representative H&E stained images from diaphragm.