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cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform.

Publication ,  Journal Article
Nassar, R; Malouf, NN; Mao, L; Rockman, HA; Oakeley, AE; Frye, JR; Herlong, JR; Sanders, SP; Anderson, PAW
Published in: Am J Physiol Heart Circ Physiol
March 2005

Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium-dependent myocardial force development, are expressed in the human; they differ in charge and length. Their expression is regulated developmentally and is affected by disease states. Human cTnT (hcTnT) isoform effects have been examined in reconstituted myofilaments. In this study, we evaluated the modulatory effects of overexpressing one cTnT isoform on in vitro and in vivo myocardial function. A hcTnT isoform, hcTnT(1), expressed during development and in heart disease but not in the normal adult heart, was expressed in transgenic (TG) mice (1-30% of total cTnT). Maximal active tension measured in skinned myocardium decreased as a function of relative hcTnT(1) expression. The pCa at half-maximal force development, Hill coefficient, and rate of redevelopment of force did not change significantly with hcTnT(1) expression. In vivo maximum rates of rise and fall of left ventricular pressure decreased, and the half-time of isovolumic relaxation increased, with hcTnT(1) expression. Substituting total cTnT charge for hcTnT(1) expression resulted in similar conclusions. Morphometric analysis and electron microscopy revealed no differences between wild-type (non-TG) and TG myocardium. No differences in isoform expression of tropomyosin, myosin heavy chain, essential and regulatory myosin light chains (MLC), TnI, or in posttranslational modifications of mouse cTnT, cTnI, or regulatory MLC were observed. These results support the hypothesis that cTnT isoform amino-terminal differences affect myofilament function and suggest that hcTnT(1) expression levels present during human development and in human heart disease can affect in vivo ventricular function.

Duke Scholars

Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

March 2005

Volume

288

Issue

3

Start / End Page

H1147 / H1156

Location

United States

Related Subject Headings

  • Ventricular Pressure
  • Ventricular Function, Left
  • Troponin
  • Tropomyosin
  • Myocardial Contraction
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

APA
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ICMJE
MLA
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Nassar, R., Malouf, N. N., Mao, L., Rockman, H. A., Oakeley, A. E., Frye, J. R., … Anderson, P. A. W. (2005). cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform. Am J Physiol Heart Circ Physiol, 288(3), H1147–H1156. https://doi.org/10.1152/ajpheart.00140.2004
Nassar, Rashid, Nadia N. Malouf, Lan Mao, Howard A. Rockman, Annette E. Oakeley, James R. Frye, J René Herlong, Stephen P. Sanders, and Page A. W. Anderson. “cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform.Am J Physiol Heart Circ Physiol 288, no. 3 (March 2005): H1147–56. https://doi.org/10.1152/ajpheart.00140.2004.
Nassar R, Malouf NN, Mao L, Rockman HA, Oakeley AE, Frye JR, et al. cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform. Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1147–56.
Nassar, Rashid, et al. “cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform.Am J Physiol Heart Circ Physiol, vol. 288, no. 3, Mar. 2005, pp. H1147–56. Pubmed, doi:10.1152/ajpheart.00140.2004.
Nassar R, Malouf NN, Mao L, Rockman HA, Oakeley AE, Frye JR, Herlong JR, Sanders SP, Anderson PAW. cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform. Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1147–H1156.

Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

March 2005

Volume

288

Issue

3

Start / End Page

H1147 / H1156

Location

United States

Related Subject Headings

  • Ventricular Pressure
  • Ventricular Function, Left
  • Troponin
  • Tropomyosin
  • Myocardial Contraction
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male