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Article Dans Une Revue Cardiovascular Research Année : 2006

Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice

Résumé

Objective: h-Adrenergic stimulation modulates cardiac contractility through protein kinase A (PKA), which phosphorylates proteins such as troponin I (cTnI) and C-protein (cMyBP-C). The relative contributions of cTnI and cMyBP-C to the regulation of myofilament Ca 2+ sensitivity are still controversial because of difficulty in targeting specific protein phosphorylation. Recently, impaired relaxation was found in cMyBP-C-deficient mice (KO) in vivo under basal conditions and after h-adrenergic stimulation. The goal of this study was to analyse the length-dependent and PKA-dependent modulations of the cardiac contractile machinery in a mouse model lacking cMyBP-C. Methods: In the present work, we studied the PKA effect on myofilament Ca 2+ sensitivity of left ventricular skinned myocytes isolated from 5-week-and 55-week-old wild-type (WT) and cMyBP-C knockout (KO) mice at 1.9 and 2.3 Am sarcomere lengths (SL). The cTnI content and phosphorylation status were examined by Western blot analysis. Results: Without PKA stimulation and at the shorter SL, Ca 2+ sensitivity was higher in KO compared to WT. The difference disappeared at the longer SL. No difference in passive tension or maximal active tension was observed. PKA stimulation induced a desensitization of WT myofilaments at both SL but had almost no effect in KO myofilaments despite similar levels of cTnI phosphorylation. We also observed expression of slow skeletal TnI in KO animals that was not correlated with the PKA effects. Conclusion: The results suggest that cMyBP-C contributes to the regulation of cardiac contraction at short sarcomere length and that myofilament desensitization induced by PKA requires the presence of cMyBP-C and does not depend only upon TnI phosphorylation.

Dates et versions

hal-01824389 , version 1 (27-06-2018)

Identifiants

Citer

Olivier Cazorla, A. Lacampagne, Szabolcs Szilagyi, Nicolas Vignier, Guillermo Salazar, et al.. Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice. Cardiovascular Research, 2006, 69 (2), pp.370-380. ⟨10.1016/j.cardiores.2005.11.009⟩. ⟨hal-01824389⟩
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