| First Author | Tanner BCW | Year | 2021 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 320 |
| Issue | 5 | Pages | H1822-H1835 |
| PubMed ID | 33666504 | Mgi Jnum | J:313252 |
| Mgi Id | MGI:6514220 | Doi | 10.1152/ajpheart.00673.2020 |
| Citation | Tanner BCW, et al. (2021) Cardiac myosin binding protein-C phosphorylation accelerates beta-cardiac myosin detachment rate in mouse myocardium. Am J Physiol Heart Circ Physiol |
| abstractText | Cardiac myosin binding protein-C (cMyBP-C) is a thick filament protein that modulates cardiac contraction-relaxation through its phosphorylation. Phosphorylation of cMyBP-C and ablation of cMyBP-C have been shown to increase the rate of MgADP release in the acto-myosin crossbridge cycle in the intact sarcomere. The influence of cMyBP-C on Pi-dependent myosin kinetics has not yet been examined. We investigated the effect of cMyBP-C and its phosphorylation on myosin kinetics in demembranated papillary muscle strips bearing the b-cardiac myosin isoform from non-transgenic (NTGbeta) and transgenic mice lacking cMyBP-C (t/tbeta). We used quick stretch and stochastic length-perturbation analysis to characterize rates of myosin detachment and force development over 0-12 mM Pi. Protein kinase-A (PKA) treatment was applied to half the strips to probe the effect of cMyBP-C phosphorylation on Pi-sensitivity of myosin kinetics. Increasing Pi increased myosin crossbridge detachment rate similarly for muscles with and without cMyBP-C, although these rates were higher in muscle without cMyBP-C. Treating myocardial strips with PKA accelerated detachment rate when cMyBP-C was present over all Pi, but not when cMyBP-C was absent. The rate of force development increased with Pi in all muscles. However, Pi sensitivity of the rate force development was reduced when cMyBP-C was present vs. absent, suggesting that cMyBP-C inhibits Pi-dependent reversal of the power stroke or stabilizes crossbridge attachment to enhance the probability of completing the power stroke. PKA treatment reduces the role for cMyBP-C to slow myosin detachment and thus effectively accelerates b-myosin detachment in the intact myofilament lattice. |
