Direct and selective myosin-inhibition stabilizes the super-relaxed state of myosin and blunts post-tetanic potentiation in fast-skeletal muscle

Abstract

Post-tetanic potentiation (PTP) describes the acute recruitment of force that follows repetitive stimulation of striated muscle. The progressive destabilization/recruitment of myosin-heads from the thick-filament backbone, and their subsequent incomplete recovery, has been postulated as a potential mechanism for PTP in fast-twitch skeletal muscles. Paradoxical PTP enhancements have been described in various models of muscular dystrophy, suggesting that contraction-induced force amplification and thick-filament disorder play a role in the pathophysiology of injury.