Mainwood G W, Renaud J M
Can J Physiol Pharmacol. 1985 May;63(5):403-16. doi: 10.1139/y85-072.
H+ ions are generated rapidly when muscles are maximally activated. This results in an intracellular proton load. Typical proton loads in active muscles reach a level of 20-25 mumol X g-1, resulting in a fall in intracellular pH of 0.3-0.5 units in mammalian muscle and 0.6-0.8 units in frog muscle. In isolated frog muscles stimulated to fatigue a proton load of this magnitude is developed, and at the same time maximum isometric force is suppressed by 70-80%. Proton loss is slowed when external pH is kept low. This is paralleled by a slow recovery of contractile tension and seems to support the idea that suppression results from intracellular acidosis. Nonfatigued muscles subjected to similar intracellular proton loads by high CO2 levels show a suppression of maximal tension by only about 30%. This indicates that only a part of the suppression during fatigue is normally due to the direct effect of intracellular acidosis. Further evidence for a component of fatigue that is not due to intracellular acidosis is provided by the fact that some muscle preparations (rat diaphragm) can be fatigued with very little lactate accumulation and very low proton loads. Even under these conditions, a low external pH (6.2) can slow recovery of tension development 10-fold compared with normal pH (7.4). We must conclude that there are at least two components to fatigue. One, due to a direct effect of intracellular acidosis, acting directly on the myofibrils, accounts for a part of the suppression of contractile force. A second, which in many cases may be the major component, is not dependent on intracellular acidosis. This component seems to be due to a change of state in one or more of the steps of the excitation-contraction coupling process. Reversal of this state is sensitive to external pH which suggests that this component is accessible from the outside of the cell.
当肌肉最大程度激活时，H⁺离子会迅速生成。这会导致细胞内质子负荷增加。活跃肌肉中的典型质子负荷达到20 - 25 μmol×g⁻¹的水平，使哺乳动物肌肉的细胞内pH值下降0.3 - 0.5个单位，青蛙肌肉的细胞内pH值下降0.6 - 0.8个单位。在刺激至疲劳的离体青蛙肌肉中会产生如此程度的质子负荷，与此同时，最大等长力会被抑制70 - 80%。当外部pH值保持较低时，质子流失会减缓。这与收缩张力的缓慢恢复同时出现，似乎支持了抑制是由细胞内酸中毒导致的观点。通过高二氧化碳水平使非疲劳肌肉承受类似的细胞内质子负荷时，最大张力仅被抑制约30%。这表明在疲劳过程中，只有一部分抑制通常是由细胞内酸中毒的直接作用引起的。一些肌肉制剂（大鼠膈肌）可以在乳酸积累极少且质子负荷非常低的情况下疲劳，这一事实为并非由细胞内酸中毒引起的疲劳成分提供了进一步的证据。即使在这些条件下，与正常pH值（7.4）相比，低外部pH值（6.2）可使张力恢复速度减慢10倍。我们必须得出结论，疲劳至少有两个组成部分。一个是由于细胞内酸中毒的直接作用，直接作用于肌原纤维，导致收缩力的部分抑制。另一个在许多情况下可能是主要成分，不依赖于细胞内酸中毒。该成分似乎是由于兴奋 - 收缩偶联过程中一个或多个步骤的状态变化引起的。这种状态的逆转对外部pH值敏感，这表明该成分可从细胞外部影响。
