Transgenic incorporation of skeletal TnT into cardiac myofilaments blunts PKC-mediated depression of force

David E. Montgomery, Murali Chandra, Qi Quan Huang, Jian Ping Jin, R. John Solaro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Protein kinase C (PKC)-mediated phosphorylation of cardiac troponin I (cTnI) and troponin T (cTnT) has been shown to diminish maximum activation of myofilaments. The functional role of cTnI phosphorylation has been investigated. However, the impact of cTnT phosphorylation on myofilament force is not well studied. We tested the effect of endogenous PKC activation on steady-state tension development and Ca2+ sensitivity in skinned fiber bundles from transgenic (TG) mouse hearts expressing fast skeletal TnT (fsTnT), which naturally lacks the PKC sites present in cTnT. The 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment induced a 29% (46.1 ± 2.5 vs. 33.4 ± 2.6 mN/mm2) reduction in maximum tension in the nontransgenic (NTG) preparations (n = 7) and was inhibited with chelerythrine. However, TPA did not induce a change in the maximum tension in the TG preparations (n = 11). TPA induced a small but significant (P < 0.02) increase in Ca2+ sensitivity (untreated pCa50 = 5.63 ± 0.01 vs. treated pCa50 = 5.72 ± 0.01) only in TG preparations. In TG preparations, 32P incorporation was not evident in TnT and was also significantly diminished in cTnI, compared with NTG. Our data indicate that incorporation of fsTnT into the cardiac myofilament lattice blunts PKC-mediated depression of maximum tension. These data also suggest that cTnT may play an important role in amplifying the myofilament depression induced by PKC-mediated phosphorylation of cTnI.

Original languageEnglish (US)
Pages (from-to)H1011-H1018
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number3 49-3
DOIs
StatePublished - 2001

Keywords

  • Myofilament activation
  • Phosphorylation sites
  • Protein kinase C
  • Troponin

ASJC Scopus subject areas

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

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