It is controversial whether the phosphate (Pi) release step in the cross-bridge cycle occurs before or after the first tension-generating step and whether it is fast or slow. We have therefore modified our previous model of the frog cross-bridge cycle by including a Pi release step either before (model A) or after (model B) the first tension-generating step and refined the two models by downhill simplex runs against experimental data for the force-velocity relation and the tension transients after length steps. Pi release step was initially made slow (70 s-1), but after refinement, it became fast (∼500 s-1 for model A and ∼6000 s-1 for model B). The two models gave similar fits to the experimental tension transients after length steps, but model A gave a better fit to the lengthening limb of the force-velocity relation than model B. 50 mM Pi inhibited the isometric tension of model A by ∼50% but that of model B by only ∼25%. The half-inhibition was at 6.0 mM Pi for model A and at 1.6 mM Pi for model B. The values for model A were consistent with experimental data. We also simulated the effect Pi jump as in caged Pi experiments. For model A, a Pi jump induced a tension fall at a rate similar to the experimental phase II. There was then a small rise in tension to the steady state mimicking the experimental phase III. The initial tension fall was caused by detachment of M⋅ADP⋅Pi myosin heads from actin and reversal of the first tension-generating step. For model B, the fall in tension was more rapid and due to reversal of the first tension-generating step, and phase III was not observed. We conclude that, as in model A, the Pi release step is before the first tension-generating step and is moderately fast.

中文翻译：

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肌肉横桥循环中磷酸盐释放步骤的位置和速率

跨桥循环中的磷酸盐（Pi）释放步骤发生在第一个张力产生步骤之前还是之后，以及它是快还是慢，这是有争议的。因此，我们通过在第一个张力生成步骤之前（模型 A）或之后（模型 B）包括一个 Pi 释放步骤来修改我们之前的青蛙横桥循环模型，并通过下坡单纯形运行对实验数据进行改进对于力-速度关系和长度步长后的张力瞬变。Pi 释放步骤最初很慢（70 s-1），但经过改进后，它变得很快（模型 A 为~500 s-1，模型 B 为~6000 s-1）。两个模型对长度步长后的实验张力瞬变给出了相似的拟合，但模型 A 比模型 B 更适合于力-速度关系的延长肢。50 mM Pi 抑制模型 A 的等长张力约 50%，但仅抑制模型 B 的等长张力约 25%。模型 A 的半抑制为 6.0 mM Pi，模型 B 的半抑制为 1.6 mM Pi。模型 A 的值与实验数据一致。我们还模拟了笼式 Pi 实验中 Pi 跳跃的效果。对于模型 A，Pi 跳跃引起张力下降，其速度与实验阶段 II 相似。然后模拟实验阶段 III 的张力小幅上升到稳态。初始张力下降是由 M⋅ADP⋅Pi 肌球蛋白头从肌动蛋白上脱离和第一个张力产生步骤的逆转引起的。对于模型 B，由于第一个张力产生步骤的逆转，张力下降更快，并且没有观察到第三阶段。我们得出的结论是，在模型 A 中，