The Ca2+ sensitizer CK‐2066260 increases myofibrillar Ca2+ sensitivity and submaximal force selectively in fast skeletal muscle

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12127-list-0001">We report that the small molecule CK‐2066260 selectively slows the off‐rate of Ca^{2 +} from fast skeletal muscle troponin, leading to increased myofibrillar Ca^{2 +} sensitivity in fast skeletal muscle.Rodents dosed with CK‐2066260 show increased hindlimb muscle force and power in response to submaximal rates of nerve stimulation in situ.CK‐2066260 has no effect on free cytosolic [Ca^{2 +}] during contractions of isolated muscle fibres.We conclude that fast skeletal muscle troponin sensitizers constitute a potential therapy to address an unmet need of improving muscle function in conditions of weakness and premature muscle fatigue.