Key result
In relaxed rat skeletal muscle, myosin exhibits two distinct ATP hydrolysis rates differing 5-fold, with the slower super relaxed rate localized predominantly to the sarcomere C-zone.
Why the study?
Myosin in relaxed muscle continues to slowly hydrolyze ATP, but direct imaging of single-molecule ATP turnover rates and localization in resting muscle sarcomeres remained to be characterized.
Super relaxed skeletal muscle myosin is stabilized by Myosin-Binding Protein C and localized to the C-zone, and this inhibited state can be pharmacologically enhanced by Mavacamten.
Answers are grounded in this paper and cite their sources.
Questions uniform myosin ATPase rates in relaxed sarcomeres; leaves open functional consequences for muscle energetics.
Muscle contraction is driven by sarcomere shortening and powered by cyclic hydrolysis of ATP by myosin molecular motors. However, myosin in relaxed muscle continues to slowly hydrolyze ATP, analogous to an idling engine. Utilizing super-resolution microscopy to directly image single molecule fluorescent ATP turnover in relaxed rat soleus skeletal muscle sarcomeres, we observed two rates of myosin ATP consumption that differed 5-fold. These distinct hydrolysis rates were spatially segregated, with the slower or “super relaxed” rate localized predominantly to the sarcomere C-zone, where Myosin Binding Protein-C (MyBP-C), a known modulator of muscle contractile function, exists. This super relaxed hydrolysis rate and its location suggest that MyBP-C can sequester myosin motors to regulate muscle metabolism and heat production in resting muscle and force generation upon activation. One Sentence Summary Super relaxed skeletal muscle myosin is stabilized by Myosin-Binding Protein C as imaged by single ATP molecule consumption.
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Nelson et al. (2020) studied Resting Skeletal Muscle. Super-resolution microscopy of single ATP molecule consumption was evaluated on Myosin ATP consumption rates. In relaxed rat skeletal muscle, myosin exhibits two distinct ATP hydrolysis rates differing 5-fold, with the slower super relaxed rate localized predominantly to the sarcomere C-zone.
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