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Effects of pseudo-phosphorylated rat cardiac troponin T are differently modulated by α- and β-myosin heavy chain isoforms

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Abstract

Interplay between the protein kinase C (PKC)-mediated phosphorylation of troponin T (TnT)- and myosin heavy chain (MHC)-mediated effects on thin filaments takes on a new significance because: (1) there is significant interaction between the TnT- and MHC-mediated effects on cardiac thin filaments; (2) although the phosphorylation of TnT by PKC isoforms is common to both human and rodent hearts, human hearts predominantly express β-MHC while rodent hearts predominantly express α-MHC. Therefore, we tested how α- and β-MHC isoforms differently affected the functional effects of phosphorylated TnT. Contractile measurements were made on cardiac muscle fibers from normal rats (α-MHC) and propylthiouracil-treated rats (β-MHC), reconstituted with the recombinant phosphomimetic-TnT (T204E; threonine 204 replaced by glutamate). Ca2+-activated maximal tension decreased differently in α-MHC + T204E (~68 %) and β-MHC + T204E (~35 %). However, myofilament Ca2+ sensitivity decreased similarly in α-MHC + T204E and β-MHC + T204E, demonstrating that a decrease in Ca2+ sensitivity alone cannot explain the greater attenuation of tension in α-MHC + T204E. Interestingly, dynamic contractile parameters (rates of tension redevelopment, crossbridge (XB) recruitment dynamics, XB distortion dynamics, and XB detachment kinetics) decreased only in α-MHC + T204E. Thus, the transition of thin filaments from the blocked- to closed-state was attenuated in α-MHC + T204E and β-MHC + T204E, but the closed- to open-state transition was attenuated only in α-MHC + T204E. Our study demonstrates that the effects of phosphorylated TnT and MHC isoforms interact to bring about different functional states of cardiac thin filaments.

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Acknowledgments

This work was funded by National Heart, Lung, and Blood Institute Grant R01-HL-075643 to Dr. Murali Chandra and a Poncin Fellowship to John Jeshurun Michael.

Conflict of interest

The authors declare that they have no conflict of interest. Our manuscript does not contain any clinical studies or patient data.

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  1. Department of Integrative Physiology and Neuroscience (Formerly VCAPP), Washington State University, 205 Veterinary Biomedical Research Building, Pullman, WA, 99164-7620, USA

    John Jeshurun Michael, Sampath K. Gollapudi & Murali Chandra

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Correspondence to Murali Chandra.

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Michael, J.J., Gollapudi, S.K. & Chandra, M. Effects of pseudo-phosphorylated rat cardiac troponin T are differently modulated by α- and β-myosin heavy chain isoforms. Basic Res Cardiol 109, 442 (2014). https://doi.org/10.1007/s00395-014-0442-9

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