Physiological significance of troponin T binding domains in striated muscle tropomyosin

Ganapathy Jagatheesan, Sudarsan Rajan, Natalia Petrashevskaya, Arnold Schwartz, Greg Boivin, Grace Arteaga, Pieter P. De Tombe, R. John Solaro, David F. Wieczorek

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Striated muscle tropomyosin (TM) plays an essential role in sarcomeric contraction and relaxation through its regulated movement on the thin filament. Previous work in our laboratory established that α-and β-TM isoforms elicit physiological differences in sarcomeric performance. To address the significance of isoform-specific troponin T binding regions in TM, in this present work we replaced α-TM amino acids 175-190 and 258-284 with the β-TM regions and expressed this chimeric protein in the hearts of transgenic mice. Hearts that express this chimeric protein exhibit significant decreases in rates of contraction and relaxation when assessed by ex vivo work-performing cardiac analyses. There are increases in time to peak pressure and in half-time to relaxation. These hearts respond appropriately to β-adrenergic stimulation but do not attain control rates of contraction or relaxation. With increased expression of the transgene, 70% of the mice die by 5 mo of age without exhibiting gross pathological changes in the heart. Myofilaments from these mice have no differences in Ca2+ sensitivity of percent maximum force, but there is a decrease in maximum tension development. Our data are the first to demonstrate that the troponin T binding regions of specific TM isoforms can alter sarcomeric performance without changing the Ca2+ sensitivity of the myofilaments.

Original languageEnglish (US)
Pages (from-to)H1484-H1494
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number4 56-4
DOIs
StatePublished - Oct 1 2004

Keywords

  • Cardiac muscle
  • Heart
  • Thin filament regulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Jagatheesan, G., Rajan, S., Petrashevskaya, N., Schwartz, A., Boivin, G., Arteaga, G., De Tombe, P. P., Solaro, R. J., & Wieczorek, D. F. (2004). Physiological significance of troponin T binding domains in striated muscle tropomyosin. American Journal of Physiology - Heart and Circulatory Physiology, 287(4 56-4), H1484-H1494. https://doi.org/10.1152/ajpheart.01112.2003