Key result
Omecamtiv mecarbil stabilizes the ON state of the thick filament but inhibits contractility at high calcium concentrations, whereas blebbistatin inhibits contractility by stabilizing the OFF state.
Omecamtiv mecarbil and blebbistatin modulate cardiac contractility by perturbing the regulatory state of the myosin thick filament, providing mechanistic insights into thick filament regulation as a therapeutic target.
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Thick filament regulation emerges as a contractility target; animal data leave open human translation.
Kampourakis et al. (2017) studied demembranated cardiac muscle cells. Omecamtiv mecarbil and blebbistatin was evaluated on Isometric force, ATP utilization, and in situ structural changes. Omecamtiv mecarbil stabilizes the ON state of the thick filament but inhibits contractility at high calcium concentrations, whereas blebbistatin inhibits contractility by stabilizing the OFF state.
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