Hypertrophic and Dilated Cardiomyopathy-Associated Troponin T Mutations R130C and ΔK210 Oppositely Affect Length-Dependent Calcium Sensitivity of Force Generation

Figures

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  FIGURE 1. Resting, maximum and calcium-dependent force generation of skinned fibers exchanged for human hcTn containing HCM-associated hcTnTR130C (n = 18 fibers), hcTnTWT (n = 19 fibers), or DCM-associated hcTnTΔK210 (n = 19 fibers). (A) Resting tension measured in relaxing solution (pCa 7) at short (1.1 L0) and long (1.25 L0) fiber length. (B) Maximum tension measured at pCa 4.28. (C) Force-pCa relations at short fiber length (1.1 L0) and long fiber length (1.25 L0). Normalized force is scaled as percentage from 0% for resting tension to 100% for maximum tension. ###Indicates highly significant different to 1.1 L0 in paired Bonferroni post tests.

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  FIGURE 2. Length-dependent parameters and parameter changes of calcium-dependent force generation of hcTn-exchanged skinned fibers. HCM: fibers containing hcTnTR130C (black circles and bars), WT: fibers containing hcTnTWT (white circles and bars), DCM: fibers containing hcTnTΔK210 (gray circles and bars). (A) Calcium sensitivity is expressed by the pCa50 required for half-maximum increase of calcium-dependent force generation. (B) Cooperativity of calcium-dependent force generation is expressed by the Hill coefficient nH of force-pCa relations. (C) Change of pCa50 and Hill coefficient nH induced by lengthening the fiber from 1.1 L0 to 1.25 L0. (D) Change of normalized force at the respective pCa induced by lengthening the fiber from 1.1 L0 to 1.25 L0. Change (delta) of parameters in (C,D) are calculated by subtracting for each fiber the parameter value at 1.1 L0 from the parameter value at 1.25 L0. Significant change of parameter (delta different from zero) is indicated by #P < 0.05, ##P < 0.01, ###(P < 0.001). Asterisks indicate significant differences *P < 0.05, **P < 0.01, ***P < 0.001 between the hcTnT-types in Tukey’s multiple comparison post-tests. For sake of clarity, only the…