Research Article

Micromechanical Thermal Assays of Ca2+-Regulated Thin-Filament Function and Modulation by Hypertrophic Cardiomyopathy Mutants of Human Cardiac Troponin

Figure 4

Influence of FHC-linked mutations in human cardiac troponin on temperature dependence of thin-filament sliding at pCa 5. Thin filaments were reconstituted with α-Tm and either rhcTn WT (circles, black), rhcTn TnI,R145G (triangles, green), rhcTn TnI,K206Q (squares, yellow), or rhcTn TnT, R278C (diamonds, blue). Data were obtained during the heating phases of multiple heating/cooling cycles, as in Figure 1; note that WT data were replotted from Figure 2(b). (a) Points represent the mean sliding speed for 3–8 filaments during 1 s. Note that speeds with TnI mutant K206Q [32] and TnT mutant R278C were generally elevated over WT. (b) Arrhenius analysis of data from (a). Symbols and colors as in (a); unregulated F-actin from the same series of experiments (Figure 2(b)) was also included in (b) (inverted triangle and dashed lines; light gray). Each dataset was fit by two linear regressions after omitting data above ~60°C (WT), ~54°C (cTnI R145G), ~51.5°C (cTnI K206Q), or ~55°C (cTnT R278C). Regression lines are shown without correction for temperature-dependent changes in solvent viscosity; points correspond to 𝑇 𝑡 , the intersection of each pair of lines. Filament sliding speeds are expressed in μm s−1.
657523.fig.004a
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657523.fig.004b
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