EMD-57033 Augments the Contractility in Porcine Myocardium by Promoting the Activation of Myosin in Thick Filaments

Figures

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  Figure 1. Permeabilized porcine myocardium mechanics with EMD treatment. (A) Active tension in a function of calcium concentration in the absence (black) and presence (blue) of 10 uM EMD (EMD). Tension under the maximally activated (Tmax) condition (B), the concentration of calcium to achieve the half-maximal activation (EC 50) (C) and Hill coefficient (nH) of the tension calcium relationship (D) before and after the EMD treatment. ns: not significant, ** p < 0.01. # p < 0.000001.

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  Figure 2. Mant-ATP assay from the permeabilized porcine myocardium before and after the EMD treatment. (A) Time course of the mant-ATP dissociation over time curves in the absence (black) and presence (blue) of 10 uM. (B) Area under the curve (AUC) of the mant-ATP dissociation time course (through 1000 s) before and after the EMD treatment. (C) The percentage of myosin heads in the SRX state (% SRX) before and after the EMD treatment. (D) The time constant of the fast phase (T1) before and after the EMD treatment. (E): The time constant of the slow phase (T2) before and after the EMD treatment. ns: not significant, * p < 0.05, ** p < 0.01.

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  Figure 3. Effects of EMD on the equatorial reflections on the permeabilized pig myocardium. (A) Two dimensional diffraction pattern from the permeabilized resting pig myocardium in the absence (Ctrl, top half) and presence of 10 μM (bottom left) and 50 μM (bottom right) ,of EMD. (B) Equatorial intensity ratio from the permeabilized pig myocardium in the absence and presence of 10 μM and 50 μM EMD. (C) Lattice spacing from the permeabilized pig myocardium in the absence and presence of 10 μM and 50 μM EMD. ** p < 0.01, *** p < 0.001.

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  Figure 4. Effects of EMD on the myosin layer lines and the meridional reflections on the permeabilized pig myocardium. (A) Intensity of the first order myosin-based layer lines (IMLL1) from the permeabilized resting pig myocardium in the absence and presence of 10 μM and 50 μM EMD. (B) Intensity of the third order myosin meridional reflections (IM3) in the absence and presence of 10 μM and 50 μM EMD. (C) Spacing of the sixth order myosin meridional (SM6) in the presence and absence of 10 μM and 50 μM EMD. (D) Intensity of the third order troponin meridional reflections (ITn3) in the presence and absence of 10 μM and 50 μM EMD. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.