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 language | English (US) |
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Pages (from-to) | 363-372 |
Number of pages | 10 |
Journal | Journal of molecular and cellular cardiology |
Volume | 45 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2008 |
Externally published | Yes |
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