Cardiac troponin I phosphorylation increases the rate of cardiac muscle relaxation

Ren Zhang, Jiaju Zhao, Alan Mandveno, James D. Potter

Research output: Contribution to journalArticle

250 Scopus citations

Abstract

Cardiac troponin (Tn) I (CTnI), compared with skeletal TnI, contains extra amino acids (32 to 33) at its amino terminus, including two adjacent serine residues. These two serine residues are believed to be phosphorylated by protein kinase A (PKA) upon stimulation of the heart by β-agonists. In this study, we found that phosphorylation of a cardiac skinned muscle preparation by PKA, mainly at CTnI, results in a decrease in the Ca2+ sensitivity of muscle contraction. The pCa50 decreased by ≃0.27±0.06 pCa units upon phosphorylation. To study cardiac muscle relaxation, we used diazo-2, a photolabile Ca2+ chelator with a low Ca2+ affinity in its intact form that is converted to a high-affinity form after photolysis. We found that the rate of cardiac muscle relaxation increased from a time of half-relaxation (t( 1/2 )) = 110±10 milliseconds to (t( 1/2 )) =70±8 milliseconds after CTnI phosphorylation. This result demonstrates that CTnI phosphorylation can be linked with the increased rate of muscle relaxation in a relatively intact muscle preparation. Since CTnI phosphorylation has been shown previously to affect the Ca2+ affinity and Ca2+ off-rate of CTnC in vitro, it is likely that the faster relaxation seen here reflects faster dissociation of Ca2+ from cardiac TnC (CTnC). Model calculations show that increased dissociation of Ca2+ from CTnC, coupled with the faster uptake of Ca2+ by the sarcoplasmic reticulum stimulated by PKA phosphorylation of phospholamban, can account for the faster relaxation seen in the inotropic response of the heart to catecholamines.

Original languageEnglish (US)
Pages (from-to)1028-1035
Number of pages8
JournalCirculation research
Volume76
Issue number6
DOIs
StatePublished - Jun 1995

Keywords

  • cardiac skinned muscle
  • cardiac troponin I

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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