BPS2026 - Distinct effects of ablation of MyBP-C on relaxation kinetics of single myofibrils from fast and slow twitch muscles

Two skeletal muscle paralogs of myosin-binding protein C, namely the slow and fast skeletal ssMyBP-C and fsMyBP-C encoded by MYBPC1 and MYBPC2 genes, respectively, are differentially expressed in fast- and slow-twitch skeletal muscle fibers. Mutations in MYBPC1 and MYBPC2 have been associated with congenital myopathies, underscoring the importance of investigating the functions of these distinct paralogs. Recently, we demonstrated that acute ablation of cardiac MyBP-C in cardiac single myofibrils using our cut-and-paste approach in SpyC3 mice resulted in acceleration of both slow and fast relaxation phases. These two phases are mostly determined by cross-bridge detachment rate and sarcomere dynamics, respectively. Here, by crossing our SpyC1 ( MYBPC1 ) and SpyC2 ( MYBPC2 ) mouse lines we generated a double mutant which enabled simultaneous deletion of both skeletal paralogs in permeabilized muscle fibers. Results indicated that ablation of MyBP-C in psoas muscle (consisting mostly of the fast-twitch fibers in mice) desensitized myofibrils to calcium and shortened the duration of the linear phase. The fast phase of relaxation also appeared accelerated, but results were not statistically significant. Unlike the psoas muscle, the soleus muscle in mice exhibits a significantly greater heterogeneity in terms of fiber type, comprising approximately 37%–58% of slow-twitch fibers, and other types ranging from intermediate to fast fibers. Notably, in soleus, we did not see any effects of cMyBP-C ablation on myofibril relaxation rates. Our findings suggest that the role of MyBP-C on relaxation varies depending on fiber type and may be more significant in fast twitch muscles than slow twitch muscles.