Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity
Two articles on PainSci cite Bellinger 2008: 1. Does Epsom Salt Work? 2. Why Drink Water After Massage?
PainSci summary of Bellinger 2008: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.
“Exhausting exercise, such as that performed by a marathon runner or a long-distance cyclist, results in significant muscle damage and can impair task performance for days or weeks, although the mechanisms underlying this impairment in exercise capacity are not understood.” Lactic acid is usually blamed for “the burn” of intense exercise, but recent evidence strongly suggests that changes in the handling of calcium ions is more relevant to muscle fatigue. This (rather technical) basic physiology experiment showed that a major “calcium ion release channel” in cells walls becomes less functional as you exercise. In the authors words, exercise “results in leaky channels … that play a role in limiting exercise capacity.”
original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
During exercise, defects in calcium (Ca2+) release have been proposed to impair muscle function. Here, we show that during exercise in mice and humans, the major Ca2+ release channel required for excitation-contraction coupling (ECC) in skeletal muscle, the ryanodine receptor (RyR1), is progressively PKA-hyperphosphorylated, S-nitrosylated, and depleted of the phosphodiesterase PDE4D3 and the RyR1 stabilizing subunit calstabin1 (FKBP12), resulting in "leaky" channels that cause decreased exercise tolerance in mice. Mice with skeletal muscle-specific calstabin1 deletion or PDE4D deficiency exhibited significantly impaired exercise capacity. A small molecule (S107) that prevents depletion of calstabin1 from the RyR1 complex improved force generation and exercise capacity, reduced Ca2+-dependent neutral protease calpain activity and plasma creatine kinase levels. Taken together, these data suggest a possible mechanism by which Ca2+ leak via calstabin1-depleted RyR1 channels leads to defective Ca2+ signaling, muscle damage, and impaired exercise capacity.
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
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