PHYSIOLOGY SHORTS: Hypochlorous acid exposure impairs skeletal muscle function and Ca2+ signalling

In this Physiology Shorts, Thomas A. Lea of School of Human Sciences, University of Western Australia, Perth, Western Australia, Australia, discusses their recent paper: Hypochlorous acid exposure impairs skeletal muscle function and Ca2+ signalling: implications for Duchenne muscular dystrophy pathology.
Read more in The Journal of Physiology: Hypochlorous acid exposure impairs skeletal muscle function and Ca2+ signalling: implications for Duchenne muscular dystrophy pathology
Thomas A. Lea et al.
601 (23), pp. 5257-5275
physoc.onlinelibrary.wiley.co...
Transcript:
Hi, I’m Dr. Tom Lea and I am a lecturer here at the University of Western Australia and I’m also a member of the skeletal muscle physiology lab group. In our lab group, we are particularly interested in the pathophysiology of skeletal muscle diseases such as Duchenne muscular dystrophy and that is what our paper is focused on, particularly the involvement of hypochlorous acid, a highly reactive oxidant, in the disease pathology of Duchenne muscular dystrophy.
The exact mechanisms of muscle damage in DMD remain largely unresolved. However, we do know that there are a few key hallmarks of the pathology which are chronic inflammation, increased reactive oxygen species production and increased cytosolic calcium, which all interact in such a way which is currently unclear to lead to the bouts of muscle necrosis which are seen in DMD. We’ve hypothesised that hypochlorous acid might be a key linking factor between these hallmarks. In our study, we isolated whole EDL muscles from wildtype and dystrophic mice. We found that hypochlorous acid induces a significant reduction in the relative maximal force in these whole muscles. We also found that in single muscle cells, hypochlorous acid could lead to an increase in resting calcium which could be largely prevented by the ryanodine receptor blocker, tetracaine. A similar effect was seen when we blocked TRP channels with gadolinium. These results indicated that hypochlorous acid was likely targeting TRP channels and ryanodine receptors.
These results combined with many others in our paper suggest a potential mechanism for hypochlorous acid mediated muscle weakness in DMD where due to the chronic inflammation, the increased expression of neutrophils leads to increased myeloperoxidase expression and thus increased expression of hypochlorous acid. This hypochlorous acid could potentially oxidise TRP channels and ryanodine receptors to lead to increases in cytosolic calcium which are characteristic of the DMD pathology. These results suggest that production of hypochlorous acid could be a potential therapeutic target for future treatments. If you’re interested in reading more, this is our paper in the Journal of Physiology which you can find in volume 601, issue 23. If you have any questions, please do not hesitate to contact me on my email here. Thank you for your time.