Favero T G, Zable A C, Bowman M B, Thompson A, Abramson J J
Department of Biology, University of Portland 97203, Oregon, USA.
J Appl Physiol (1985). 1995 May;78(5):1665-72. doi: 10.1152/jappl.1995.78.5.1665.
Sarcoplasmic reticulum (SR) Ca2+ release channel function is modified by ligands (Mg2+, Ca2+, ATP, and H+) that are generated during a bout of exercise. We have examined the effects of changing intracellular metabolites on Ca2+ release, [3H]ryanodine binding, and single-Ca2+ release channel activity of SR isolated from white rabbit skeletal muscle. Increasing Mg2+ (from 0 to 4 mM) and decreasing pH (7.1-6.5) inhibited SR Ca2+ release and [3H]-ryanodine binding. In addition, increasing lactate concentrations from 2 to 20 mM inhibited [3H]ryanodine binding to SR vesicles, inhibited SR Ca2+ release, and decreased the single-channel open probability. These findings suggest that intracellular modifications that disrupt excitation-contraction coupling and decrease Ca2+ transients will promote a decline in tension development and contribute to muscle fatigue. In addition, we show that hydrogen peroxide induces Ca2+ release and increases [3H]ryanodine binding to its receptor, suggesting that reactive oxygen species produced during exercise may compromise muscle function by altering the normal gating of the SR Ca2+ release channel.
肌浆网（SR）Ca2+释放通道的功能会受到运动期间产生的配体（Mg2+、Ca2+、ATP和H+）的影响。我们研究了改变细胞内代谢产物对从白兔骨骼肌分离出的SR的Ca2+释放、[3H]ryanodine结合以及单Ca2+释放通道活性的影响。增加Mg2+（从0到4 mM）和降低pH（7.1 - 6.5）会抑制SR的Ca2+释放和[3H] - ryanodine结合。此外，将乳酸浓度从2 mM增加到20 mM会抑制[3H]ryanodine与SR囊泡的结合，抑制SR的Ca2+释放，并降低单通道开放概率。这些发现表明，破坏兴奋 - 收缩偶联并减少Ca2+瞬变的细胞内变化将导致张力发展下降并导致肌肉疲劳。此外，我们表明过氧化氢会诱导Ca2+释放并增加[3H]ryanodine与其受体的结合，这表明运动期间产生的活性氧可能通过改变SR Ca2+释放通道的正常门控来损害肌肉功能。
