| First Author | Pohlmann L | Year | 2007 |
| Journal | Circ Res | Volume | 101 |
| Issue | 9 | Pages | 928-38 |
| PubMed ID | 17823372 | Mgi Jnum | J:141337 |
| Mgi Id | MGI:3818133 | Doi | 10.1161/CIRCRESAHA.107.158774 |
| Citation | Pohlmann L, et al. (2007) Cardiac myosin-binding protein C is required for complete relaxation in intact myocytes. Circ Res 101(9):928-38 |
| abstractText | 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 Ca2+ 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 Ca2+. 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 Ca2+ and SL showed that KO cells started to contract at lower Ca2+ without reaching a higher maximum, yielding a smaller area of the phase-plane diagram. Both sarcomere shortening and Ca2+ transient were prolonged in KO. Isolated KO left atria exhibited a marked increase in sensitivity to external Ca2+ and, in contrast to WT, continued to develop twitch force at low micromolar Ca2+. 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 Ca2+ sensitivity. Our findings indicate that cMyBP-C functions as a restraint on myosin-actin interaction at low Ca2+ and short SL to allow complete relaxation during diastole. |
