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- W2029598839 abstract "Divergent effects of α– and β–myosin heavy chain (MHC) isoforms on contractile behavior arise mainly because of their impact on thin filament cooperativity. The N terminus of cardiac troponin T (cTnT) also modulates thin filament cooperativity. Our hypothesis is that the impact of the N terminus of cTnT on thin filament activation is modulated by a shift from α- to β-MHC isoform. We engineered two recombinant proteins by deleting residues 1–43 and 44–73 in rat cTnT (RcTnT): RcTnT1–43Δ and RcTnT44–73Δ, respectively. Dynamic and steady-state contractile parameters were measured at sarcomere length of 2.3 µm after reconstituting proteins into detergent-skinned muscle fibers from normal (α-MHC) and propylthiouracil-treated (β-MHC) rat hearts. α-MHC attenuated Ca2+-activated maximal tension (∼46%) in RcTnT1–43Δ fibers. In contrast, β-MHC decreased tension only by 19% in RcTnT1–43Δ fibers. Both α- and β-MHC did not affect tension in RcTnT44–73Δ fibers. The instantaneous muscle fiber stiffness measurements corroborated the divergent impact of α- and β-MHC on tension in RcTnT1–43Δ fibers. pCa50 (-log of [Ca2+]free required for half-maximal activation) decreased significantly by 0.13 pCa units in α-MHC + RcTnT1–43Δ fibers but remained unaltered in β-MHC + RcTnT1–43Δ fibers, demonstrating that β-MHC counteracted the attenuating effect of RcTnT1–43Δ on myofilament Ca2+ sensitivity. β-MHC did not alter the sudden stretch–mediated recruitment of new cross-bridges (ER) in RcTnT1–43Δ fibers, but α-MHC attenuated ER by 36% in RcTnT1–43Δ fibers. The divergent impact of α- and β-MHC on how the N terminus of cTnT modulates contractile dynamics has implications for heart disease; alterations in cTnT and MHC are known to occur via changes in isoform expression or mutations." @default.
- W2029598839 created "2016-06-24" @default.
- W2029598839 creator A5054044055 @default.
- W2029598839 creator A5083588359 @default.
- W2029598839 date "2013-09-16" @default.
- W2029598839 modified "2023-10-17" @default.
- W2029598839 title "Divergent effects of α- and β-myosin heavy chain isoforms on the N terminus of rat cardiac troponin T" @default.
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- W2029598839 doi "https://doi.org/10.1085/jgp.201310971" @default.
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