Myosin from the ventricle is more sensitive to omecamtiv mecarbil than myosin from the atrium

Omecamtiv mecarbil (OM), an activator of cardiac myosin, strongly affects contractile characteristics of the ventricles and, to a much lesser extent, the characteristics of atrial contraction. We compared the molecular mechanism of action of OM on the interaction of atrial and ventricular myosin with actin using an optical trap and an in vitro motility assay. In concentrations up to 0.5 μM, OM did not affect the step size of a myosin molecule but reduced it at a higher OM level. OM substantially prolonged the interaction of both isoforms of myosin with actin. However, the interaction characteristics of ventricular myosin with actin were more sensitive to OM than those of atrial myosin. Our results, obtained at the level of isolated proteins, can explain why the impact of OM in therapeutic concentrations on the contractile function of the atrium is less significant as compared to those of the ventricle. •OM reduces the step size of atrial and ventricular myosin.•OM increases substantially the interaction of cardiac isomyosins with actin.•Ventricular myosin is more sensitive to OM than atrial myosin.•This explains why the OM impact on atrial function is less than on ventricular one.