The functional properties of human slow skeletal troponin T isoforms in cardiac muscle regulation

J Biol Chem. 2012 Oct 26;287(44):37362-70. doi: 10.1074/jbc.M112.364927. Epub 2012 Sep 12.


Human slow skeletal troponin T (HSSTnT) shares a high degree of homology with cardiac TnT (CTnT). Although the presence of HSSTnT has not been confirmed in the heart at the protein level, detectable levels of HSSTnT mRNA have been found. Whether HSSTnT isoforms are expressed transiently remains unknown. Because transient re-expression of HSSTnT may be a potential mechanism of regulating function, we explored the effect of HSSTnT on the regulation of cardiac muscle. At least three HSSTnT isoforms have been found to exist in slow skeletal muscle: HSSTnT1 (+exons 5 and 12), HSSTnT2 (+exon 5, -exon 12), and HSSTnT3 (-exons 5 and 12). Another isoform, HSSTnT hypothetical (Hyp) (-exon 5, +exon 12), has only been found at the mRNA level. Compared with HCTnT3 (adult isoform), Tn complexes containing HSSTnT1, -2, and -3 did not alter the actomyosin ATPase activation and inhibition in the presence and absence of Ca(2+), respectively. HSSTnTHyp was not evaluated as it did not form a Tn complex under a variety of conditions. Porcine papillary skinned fibers displaced with HSSTnT1, -2, or -3 and reconstituted with human cardiac troponin I and troponin C (HCTnI·TnC) complex showed a decrease in the Ca(2+) sensitivity of force development and an increase in maximal recovered force (HSSTnT1 and -3) compared with HCTnT3. In contrast, HSSTnTHyp showed an increase in the Ca(2+) sensitivity of force development. This suggests that re- or overexpression of specific SSTnT isoforms might have therapeutic potential in the failing heart because they increase the maximal force of contraction. In addition, circular dichroism and proteolytic digestion experiments revealed structural differences between HSSTnT isoforms and HCTnT3 and that HSSTnT1 is more susceptible to calpain and trypsin proteolysis than the other HSSTnTs. Overall, HSSTnT isoforms despite being homologues of CTnT may display distinct functional properties in muscle regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / physiology
  • Calpain / chemistry
  • Circular Dichroism
  • Humans
  • In Vitro Techniques
  • Myocardial Contraction*
  • Myocardium / cytology*
  • Myocardium / enzymology
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology*
  • Myosins / metabolism
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Isoforms / physiology
  • Protein Structure, Secondary
  • Proteolysis
  • Sus scrofa
  • Troponin T / chemistry
  • Troponin T / metabolism
  • Troponin T / physiology*
  • Trypsin / chemistry


  • Protein Isoforms
  • TNNT3 protein, human
  • Troponin T
  • Trypsin
  • Calpain
  • Myosins
  • Calcium