The effect of omecamtiv mecarbil on actin-myosin interaction in the disused rat soleus muscle

Abstract

Preventing muscle atrophy caused by disuse is a major concern in space, clinical, and rehabilitation medicine. This study aimed to attenuate the impact of disuse and support muscle function during hindlimb unloading using the β-myosin activator omecamtiv mecarbil (OM). We obtained soleus muscle myosin from rats in control, control with 10-day OM supplementation, hindlimb-unloaded, and hindlimb-unloaded with 10-day OM supplementation (prolonged treatment). To examine the direct effect of OM (direct treatment) on myosin from all groups, we added it to myosin in the flow cell at a concentration of 1 μM. Using an in vitro motility assay, we examined the sliding velocity of actin filaments and regulated thin filaments over soleus muscle myosin, the fraction of motile filaments, calcium sensitivity and Hill coefficient in the “pCa-velocity” and “pCa-fraction of motile filaments” relationships, relative force. Hindlimb unloading resulted in a slow-to-fast shift in the content of myosin heavy and light chains isoforms, an increased sliding velocity of actin filaments and regulated thin filaments over myosin. 10-day OM supplementation decreased the sliding velocity of actin filaments and regulated thin filaments over myosin slightly increasing calcium sensitivity in healthy rats and prevented the increase in the velocity caused by disuse without altering relative force, myosin isoform content. Direct treatment reduced the sliding velocity of actin filaments and regulated thin filaments over myosin while enhancing calcium sensitivity and relative force in all studied groups. Thus, both direct and prolonged OM treatment mitigated the effects of disuse on the functional characteristics of soleus muscle myosin.