Cardiac troponin I and tension generation of skinned fibres in the developing rat heart

J Mol Cell Cardiol. 1994 Sep;26(9):1123-31. doi: 10.1006/jmcc.1994.1131.

Abstract

During development of the myocardium the troponin I (TNI) isoform expression is switched from a cAMP-insensitive, slow skeletal muscle TNI to a cAMP-sensitive, cardiac TNI isoform (cTNI). To study the functional consequence of alterations in cTNI expression in the rat heart we investigated the cAMP-controlled cTNI phosphorylation in comparison with alterations of functional properties of isolated cardiac myofibrils during the first postnatal month. cTNI was identified by Western blot analysis followed by a semiquantitative assessment. From the third to the 28th postnatal day the relative concentrations of the cardiac isoform of TNI increased 2.9 +/- 0.3-fold. In the same period the amount of phosphate incorporated into cTNI in the presence of exogenous cAMP-dependent protein kinase (PKA) and 32P[gamma]-ATP was increased 5.8 +/- 0.2-fold (24.2 +/- 3.5 v 140.2 +/- 7.6 pmolP/mg protein loaded onto the gel) whereas the phosphorylation of C-protein was only increased 1.6 +/- 0.2-fold. Ca(2+)-activated isometric tension generation of skinned heart fibres measured in the range of pCa from 6 to 4.5 was not affected by PKA at day 3. However, isometric tension generation of fibres prepared from 28-day-old rats was suppressed by incubation with PKA which was accompanied by a rightward shift in the force/pCa relation. Under these conditions half-maximal tension development was found at pCa 5.38 v 5.52 (p < 0.05) in the absence of PKA. The Ca2+ sensitivity of the contractile apparatus was not affected by PKA-induced phosphorylation of C-protein. These data give direct evidence for the physiological relevance of the onset of cAMP-induced phosphorylation of cTNI for the Ca(2+)-activated tension generation in cardiac myofibrils during postnatal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Heart / drug effects
  • Heart / growth & development
  • In Vitro Techniques
  • Myocardial Contraction / physiology*
  • Myocardium / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Troponin / metabolism*
  • Troponin I

Substances

  • Troponin
  • Troponin I
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium