BACKGROUND AND PURPOSE: Omecamtiv mecarbil (OM) is a novel cardiac myosin 
activator drug for inotropic support in systolic heart failure. Here we have 
assessed the concentration-dependent mechanical effects of OM in permeabilized 
cardiomyocyte-sized preparations and single skeletal muscle fibres of 
Wistar-Kyoto rats under isometric conditions.
EXPERIMENTAL APPROACHES: Ca2+ -dependent active force production (Factive ), its 
Ca2+ sensitivity (pCa50 ), the kinetic characteristics of Ca2+ -regulated 
activation and relaxation, and Ca2+ -independent passive force (Fpassive ) were 
monitored in Triton X-100-skinned preparations with and without OM (3nM-10 μM).
KEY RESULTS: In permeabilized cardiomyocytes, OM increased the Ca2+ sensitivity 
of force production (ΔpCa50 : 0.11 or 0.34 at 0.1 or 1 μM respectively). The 
concentration-response relationship of the Ca2+ sensitization was bell-shaped, 
with maximal effects at 0.3-1 μM OM (EC50 : 0.08 ± 0.01 μM). The kinetics of 
force development and relaxation slowed progressively with increasing OM 
concentration. Moreover, OM increased Fpassive in the cardiomyocytes with an 
apparent EC50 value of 0.26 ± 0.11 μM. OM-evoked effects in the diaphragm muscle 
fibres with intrinsically slow kinetics were largely similar to those in 
cardiomyocytes, while they were less apparent in muscle fibres with fast 
kinetics.
CONCLUSIONS AND IMPLICATIONS: OM acted as a Ca2+ -sensitizing agent with a 
downstream mechanism of action in both cardiomyocytes and diaphragm muscle 
fibres. The mechanism of action of OM is connected to slowed 
activation-relaxation kinetics and at higher OM concentrations increased 
Fpassive production.