Tropomyosin 3 expression leads to hypercontractility and attenuates myofilament length-dependent Ca2+ activation

Kathy Pieples, Grace Arteaga, R. John Solaro, Ingrid Grupp, John N. Lorenz, Greg P. Boivin, Ganapathy Jagatheesan, Erin Labitzke, Pieter P. Detombe, John P. Konhilas, Thomas C. Irving, David F. Wieczorek

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Tropomyosin (TM), an integral component of the thin filament, is encoded by three striated muscle isoforms: α-TM, β-TM, and TPM 3. Although the α-TM and β-TM isoforms are well characterized, less is known about the function of the TPM 3 isoform, which is predominantly found in the slow-twitch musculature of mammals. To determine its functional significance, we ectopically expressed this isoform in the hearts of transgenic mice. We generated six transgenic mouse lines that produce varying levels of TPM 3 message with ectopic TPM 3 protein accounting for 40-60% of the total striated muscle tropomyosin. The transgenic mice have normal life spans and exhibit no morphological abnormalities in their sarcomeres or hearts. However, there are significant functional alterations in cardiac performance. Physiological assessment of these mice by using closed-chest analyses and a work-performing model reveals a hyperdynamic effect on systolic and diastolic function. Analysis of detergent-extracted fiber bundles demonstrates a decreased sensitivity to Ca2+ in force generation and a decrease in length-dependent Ca2+ activation with no detectable change in interfilament spacing as determined by using X-ray diffraction. Our data are the first to demonstrate that TM isoforms can affect sarcomeric performance by decreasing sensitivity to Ca2+ and influencing the length-dependent Ca2+ activation.

Original languageEnglish (US)
Pages (from-to)H1344-H1353
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number4 52-4
DOIs
StatePublished - Oct 2002

Keywords

  • Cardiac muscle
  • Heart
  • Thin filament regulation

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Tropomyosin 3 expression leads to hypercontractility and attenuates myofilament length-dependent Ca<sup>2+</sup> activation'. Together they form a unique fingerprint.

Cite this