In this Physiology Shorts video, Arthur Cheng (Karolinska Institutet, Stockholm, Sweden) talks about his recent paper investigating whether a small molecule fast skeletal troponin activator (FSTA), CK‐2066260, can mitigate muscle fatigue.. Find out more in The Journal of Physiology:
Fast skeletal muscle troponin activator CK‐2066260 increases fatigue resistance by reducing the energetic cost of muscle contraction
Arthur J. Cheng, Darren T. Hwee, Leo H. Kim, Nickie Durham, Hsiao T. Yang, Aaron C. Hinken, Adam R. Kennedy, Ronald L. Terjung, Jeffrey R. Jasper, Fady I. Malik & Håkan Westerblad.
597(17), pp. 4615–4625.
Transcript:
Hi, I’m Arthur Cheng and I’d like to talk to you about our recent study published in The Journal of Physiology titled “Fast skeletal muscle troponin activator CK-2066260 increases fatigue resistance by reducing the energetic cost of muscle contraction:”
Within skeletal muscle, the major causes of fatigue are reduced sarcoplasmic reticulum calcium release and decreased myofibrillar calcium sensitivity. One of the reasons why decreased sarcoplasmic reticulum calcium release is associated with fatigue is that intracellular calcium cycling is an energy consuming process with calcium reuptake back into the sarcoplasmic reticulum accounting for a major fraction of the energy consumed by muscle during exercise. A major finding of our manuscript is that a recently developed small molecule fast skeletal muscle troponin activator, CK-2066260, or CK-260 for short, acts as a calcium sensitizer that could mitigate fatigue by reducing the amount of calcium required to produce a given force.
Thus, by lowering the requirement for the amount of intracellular calcium cycling, the energetic cost of muscle contraction was reduced, resulting in improved fatigue resistance from the single fibre level up to the in-vivo level in voluntarily exercising rodents. These results show promise in the use of fast skeletal muscle troponin activators, such as CK-260, for the treatment of muscle weakness and fatigue in a variety of diseases.
Thank you for taking the time to learn more about our study published in The Journal of Physiology. Please contact Hakan Westerblad at hakan.westerblad@ki.se, if you have any questions.
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