Murphy Richard A, Rembold Christopher M
Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Can J Physiol Pharmacol. 2005 Oct;83(10):857-64. doi: 10.1139/y05-090.
In contrast to striated muscle, both normalized force and shortening velocities are regulated functions of cross-bridge phosphorylation in smooth muscle. Physiologically this is manifested as relatively fast rates of contraction associated with transiently high levels of cross-bridge phosphorylation. In sustained contractions, Ca2+, cross-bridge phosphorylation, and ATP consumption rates fall, a phenomenon termed "latch". This review focuses on the Hai and Murphy (1988a) model that predicted the highly non-linear dependence of force on phosphorylation and a directly proportional dependence of shortening velocity on phosphorylation. This model hypothesized that (i) cross-bridge phosphorylation was obligatory for cross-bridge attachment, but also that (ii) dephosphorylation of an attached cross-bridge reduced its detachment rate. The resulting variety of cross-bridge cycles as predicted by the model could explain the observed dependencies of force and velocity on cross-bridge phosphorylation. New evidence supports modifications for more general applicability. First, myosin light chain phosphatase activity is regulated. Activation of myosin phosphatase is best demonstrated with inhibitory regulatory mechanisms acting via nitric oxide. The second modification of the model incorporates cooperativity in cross-bridge attachment to predict improved data on the dependence of force on phosphorylation. The molecular basis for cooperativity is unknown, but may involve thin filament proteins absent in striated muscle.
与横纹肌不同，平滑肌中归一化力和缩短速度都是横桥磷酸化的调节功能。在生理上，这表现为与横桥磷酸化的瞬时高水平相关的相对快速的收缩速率。在持续收缩中，Ca2+、横桥磷酸化和ATP消耗速率下降，这种现象称为“闩锁”。本综述重点关注Hai和Murphy（1988a）的模型，该模型预测了力对磷酸化的高度非线性依赖性以及缩短速度对磷酸化的直接比例依赖性。该模型假设：（i）横桥磷酸化是横桥附着所必需的，而且（ii）附着横桥的去磷酸化降低了其脱离速率。该模型预测的各种横桥循环可以解释观察到的力和速度对横桥磷酸化的依赖性。新证据支持对该模型进行修改以使其具有更广泛的适用性。首先，肌球蛋白轻链磷酸酶活性受到调节。通过一氧化氮起作用的抑制性调节机制最能证明肌球蛋白磷酸酶的激活。该模型的第二个修改是在横桥附着中纳入协同性，以预测关于力对磷酸化依赖性的改进数据。协同性的分子基础尚不清楚，但可能涉及横纹肌中不存在的细肌丝蛋白。
