Titre :
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Effects of PKA stimulation on the length-dependent activation of cardiac myosin binding protein C deficient cardiomyocytes (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Cazorla O ;
Szilagyi S ;
Vignier N ;
Kulikovskaya ;
Winegrad S ;
Vassort G ;
Carrier L ;
Lacampagne A
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 88
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Langues:
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Anglais
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Mots-clés :
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calcium
;
colloque
;
myocarde
;
myofilament
;
phosphorylation
;
protéine kinase A
;
protéine MyBP-C cardiaque
;
souris
;
troponine
;
ventricule gauche
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Résumé :
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Communication n° 551. b-adrenergic stimulation modulates cardiac contractility through protein kinase A (PKA), which phosphorylates cellular proteins, such as cardiac troponin I (cTnI) and cardiac C-protein (cMyBP-C). The relative contributions of cTnI and cMyBP-C to the regulation of myofilaments Ca2+ sensitivity are still controversial because of difficulty in targeting phosphorylation to specific proteins. In the present work we studied the PKA effect on myofilament Ca2+ sensitivity of left ventricular skinned myocytes isolated from young and old wild type mice (WT) and cMyBP-C deficient mice (KO) at two sarcomere lengths (SL: 1.9 and 2.3 µm). Without PKA stimulation and at the shorter SL, Ca2+ sensitivity was higher in KO than in WT. The difference disappeared at the longer SL. Ca2+ sensitivity at 1.9 µm SL was increased by superfusing WT skinned cells with C1C2 fragments, which are the domains of cMyBP-C that interact with myosin and should uncouple endogenous cMyBP-C from myosin. 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 on KO myofilaments. The results suggest that cMyBP-C contributes to the regulation of cardiac contraction and is required for the decrease in Ca2+ sensitivity produced by PKA.
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