Late-stage alterations in myofibrillar contractile function in a transgenic mouse model of dilated cardiomyopathy (Tgαq*44)

István Ferenc Édes, Attila Tóth, Gabor Csanyi, Magdalena Lomnicka, Stefan Chłopicki, István Édes, Zoltán Papp

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Mechanical and biochemical alterations were investigated in permeabilized cardiomyocytes along with the progression of dilated cardiomyopathy (DCM) in a transgenic mouse line overexpressing the activated Gαq protein (Tgαq*44). The isometric force, its Ca2+ sensitivity (pCa50) and the turnover rate of the actin-myosin cycle (ktr) were determined at sarcomere lengths (SLs) of 1.9 μm and 2.3 μm before (at 4 and 10 months of age) and after hemodynamic decompensation (at 14 and 18 months of age) in Tgαq*44 cardiomyocytes and in age-matched control cardiomyocytes. The SL-dependence of pCa50 was not different in Tgαq*44 and control hearts. In contrast, a significant increase in pCa50 was observed in the Tgαq*44 cardiomyocytes (ΔpCa50: 0.10-0.15 vs. the controls) after 10 months of age that could be diminished by exposures to the catalytic subunit of protein kinase A (PKA). Accordingly, a decline in endogenous PKA activity and decreased troponin I phosphorylation were detected after 10 months in the Tgαq*44 hearts. Finally, the maximal Ca2+-activated force (Fo) and ktr were lower and the passive force (Fpassive) was higher at 18 months in the Tgαq*44 cardiomyocytes compared to the control. These mechanical alterations were paralleled by a robust increase in β-myosin heavy chain expression in the Tgαq*44 hearts. In conclusion, our data suggested that an initial decrease of PKA signaling and subsequent changes in myofilament protein expression may contribute to the development of dilated cardiomyopathy in Tgαq*44 hearts.

Original languageEnglish (US)
Pages (from-to)363-372
Number of pages10
JournalJournal of molecular and cellular cardiology
Volume45
Issue number3
DOIs
StatePublished - Sep 1 2008

Fingerprint

Dilated Cardiomyopathy
Cardiac Myocytes
Transgenic Mice
Sarcomeres
Cyclic AMP-Dependent Protein Kinases
Gq-G11 GTP-Binding Protein alpha Subunits
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Troponin I
Myosin Heavy Chains
Myofibrils
Myosins
Actins
Hemodynamics
Phosphorylation
Proteins

Keywords

  • Cardiac function
  • Dilated cardiomyopathy
  • G proteins
  • Heart failure
  • Phosphorylation
  • Protein kinase A (PKA)
  • Protein kinase C
  • Transgenic mouse
  • Troponin I

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Late-stage alterations in myofibrillar contractile function in a transgenic mouse model of dilated cardiomyopathy (Tgαq*44). / Édes, István Ferenc; Tóth, Attila; Csanyi, Gabor; Lomnicka, Magdalena; Chłopicki, Stefan; Édes, István; Papp, Zoltán.

In: Journal of molecular and cellular cardiology, Vol. 45, No. 3, 01.09.2008, p. 363-372.

Research output: Contribution to journalArticle

Édes, István Ferenc ; Tóth, Attila ; Csanyi, Gabor ; Lomnicka, Magdalena ; Chłopicki, Stefan ; Édes, István ; Papp, Zoltán. / Late-stage alterations in myofibrillar contractile function in a transgenic mouse model of dilated cardiomyopathy (Tgαq*44). In: Journal of molecular and cellular cardiology. 2008 ; Vol. 45, No. 3. pp. 363-372.
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AU - Édes, István Ferenc

AU - Tóth, Attila

AU - Csanyi, Gabor

AU - Lomnicka, Magdalena

AU - Chłopicki, Stefan

AU - Édes, István

AU - Papp, Zoltán

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