The Fast Skeletal Troponin Activator, CK‐2017357, Improves Resistance to Fatigue in Healthy, Conscious Rats

Abstract

Fast skeletal muscle troponin activators, such as CK‐2017357, amplify the sub‐maximal force frequency response in ex vivo and in situ muscle studies, and decrease muscle fatigue in a rat femoral artery ligation model of vascular insufficiency. We report the effects of CK‐2017357 on running fatigue resistance in conscious, healthy rats. Treadmill running time (aerobic ). Rats were tested at 30m/min until failure; time and distance run were recorded. Oral CK‐ 2017357 at doses of 10 and 20mg/kg, significantly increased running time on the treadmill by 20% over baseline (p<0.01) and 50% over vehicle control (p<0.01). Rotarod running time (anaerobic). An accelerating rotarod was ramped between 12–25 revolutions per minute (RPM) over 10 minutes after which animals were allowed to continue at 25RPM for a further 5 minutes. CK‐2017357 increased rotarod running time by up to 2‐fold at doses of 1 and 3mg/kg (p<0.05 and p<0.01 respectively vs. vehicle control). Similar effects were seen with other fast skeletal muscle troponin activators but not with caffeine, creatine or phosphoserine. Fast skeletal troponin activators, such as CK‐2017357, seem to reduce susceptibility to fatigue in healthy rats both in a long distance, endurance assay (treadmill), and in a shorter distance, high‐intensity assay (rotarod). Thus, the mechanism of action may be useful in treating disorders that increase susceptibility to muscle fatigue.