The protein nNOS-mu, which is just one form of the nNOS protein, is essential for skeletal muscle health, and signaling via nNOS-mu is commonly reduced in neuromuscular disease. Now, Justin Percival and colleagues, at the University of Washington, Seattle, have identified a crucial role for the nNOS-beta form of nNOS in mouse skeletal muscle, where it enables skeletal muscle to maintain force production during and after exercise.
In the study, mouse muscles lacking both nNOS-beta and nNOS-mu were found to be smaller in mass, to be intrinsically weaker, to be more susceptible to fatigue, and to exhibit more marked postexercise weakness than mouse muscles lacking only nNOS-mu.
The specific function of nNOS-beta was determined to be regulation of skeletal muscle structural and functional integrity. By contrast, previous data have indicated that nNOS-mu helps match blood supply with the metabolic demands of active muscle. These distinct roles for nNOS-beta and nNOS-mu are likely a result of the fact that the authors found the two proteins at distinct locations within skeletal muscle cells; the former was localized to the Golgi apparatus and the latter to the sarcolemma.
These data indicate that nNOS proteins are critical regulators of skeletal muscle exercise performance.
The research appears in the Journal of Clinical Investigation.
- Percival et al. Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI40736
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