Troponin T isoforms modulate calcium dependence of the kinetics of the cross-bridge cycle: Studies using a transgenic mouse line

Sarah M. MacFarland, Jian Ping Jin, Frank V. Brozovich

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Alternative splicing of troponin T (TnT) in striated muscle during development results in expression of different isoforms, with the splicing of a 5′ exon of TnT resulting in the expression of low-molecular-weight basic adult TnT isoforms and high-molecular-weight acidic embryonic TnT isoforms. Although other differences exist, the main differences between cardiac TnT (cTnT) and fast skeletal muscle TnT (fTnT) are in the NH2 terminus, with fTnT being less acidic than cTnT. A transgenic mouse line expressing chicken fTnT in the heart was used to investigate the functional significance of TnT NH2-terminal charge differences on cardiac muscle contractility. The rates of force redevelopment (ktr) at four levels of Ca2+ activation were recorded for skinned left ventricular trabeculae from control and transgenic mice. The ktr vs Ca2+ relationship was different in control mice and transgenic mice, suggesting that the structure of TnT, and possibly the NH2-terminal region, is involved in determining the kinetics of cross-bridge cycle. These results suggest that isoform shifts in TnT may be an important molecular mechanism for determining the Ca2+ dependence of cardiac muscle contractility.

Original languageEnglish (US)
Pages (from-to)241-246
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume405
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Cardiac muscle
  • Force redevelopment
  • Kinetics
  • Skeletal muscle
  • Velocity of shortening

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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