Details

Autor(en) / Beteiligte

• Pohlmann, Lutz
• Kröger, Irena
• Vignier, Nicolas
• Schlossarek, Saskia
• Krämer, Elisabeth
• Coirault, Catherine
• Sultan, Karim R
• El-Armouche, Ali
• Winegrad, Saul
• Eschenhagen, Thomas
• Carrier, Lucie

Titel

Cardiac Myosin-Binding Protein C Is Required for Complete Relaxation in Intact Myocytes

Ist Teil von

• Circulation research, 2007-10, Vol.101 (9), p.928-938

Ort / Verlag

Hagerstown, MD: American Heart Association, Inc

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• The role of cardiac myosin-binding protein C (cMyBP-C) in cardiac contraction is still not fully resolved. Experimental ablation of cMyBP-C by various means resulted in inconsistent changes in Ca sensitivity and increased velocity of force of skinned preparations. To evaluate how these effects are integrated in an intact, living myocyte context, we investigated consequences of cMyBP-C ablation in ventricular myocytes and left atria from cMyBP-C knock-out (KO) mice compared with wild-type (WT). At 6 weeks, KO myocytes exhibited mild hypertrophy that became more pronounced by 30 weeks. Isolated cells from KO exhibited markedly lower diastolic sarcomere length (SL) without change in diastolic Ca. The lower SL in KO was partly abolished by the actin-myosin ATPase inhibitors 2,3-butanedione monoxime or blebbistatin, indicating residual actin-myosin interaction in diastole. The relationship between cytosolic Ca and SL showed that KO cells started to contract at lower Ca without reaching a higher maximum, yielding a smaller area of the phase-plane diagram. Both sarcomere shortening and Ca transient were prolonged in KO. Isolated KO left atria exhibited a marked increase in sensitivity to external Ca and, in contrast to WT, continued to develop twitch force at low micromolar Ca. Taken together, the main consequence of cMyBP-C ablation was a defect in diastolic relaxation and a smaller dynamic range of cell shortening, both of which likely result from the increased myofilament Ca sensitivity. Our findings indicate that cMyBP-C functions as a restraint on myosin-actin interaction at low Ca and short SL to allow complete relaxation during diastole.