CROSS-BRIDGE PHOSPHORYLATION AND REGULATION OF LATCH STATE IN SMOOTH-MUSCLE
CROSS-BRIDGE PHOSPHORYLATION AND REGULATION OF LATCH STATE IN SMOOTH-MUSCLE
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DOI：
10.1152/ajpcell.1988.254.1.c99
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发表时间：
1988-01-01
影响因子：
--
通讯作者：
MURPHY, RA
中科院分区：
文献类型：
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作者：
HAI, CM;MURPHY, RA
我们已经开发了一个最小的动力学模型的跨桥相互作用与细丝平滑肌。该模型假设了两种类型的跨桥相互作用：1）循环磷酸化跨桥和2）非循环去磷酸化跨桥（“锁桥”）。主要假设是：1）钙依赖性肌球蛋白磷酸化是唯一假定的调节机制，2）每个肌球蛋白头独立发挥作用，3）闩桥是由连接的横桥去磷酸化形成的。速率常数通过拟合肌球蛋白磷酸化和应激发展的时间进程数据来解决。速率常数的比较表明，闩桥脱离是限速步骤。模型刺激预测稳态应力肌球蛋白磷酸化的双曲线依赖性，这与完整组织中磷酸化水平低的高应力值的实验观察相对应。模型刺激也预测了实验观察，而不是初始磷酸化瞬态只加速应激发展，对最终的稳态应激水平没有影响。因为在这个模型中唯一的钙依赖性调节机制是激活肌球蛋白轻链激酶，这些结果是一致的假设，肌球蛋白磷酸化是必要的和足够的闩锁状态的发展。
We have developed a minimum kinetic model for cross-bridge interactions with the thin filament in smooth muscle. The model hypothesizes two types of cross-bridge interactions: 1) cycling phosphorylated cross bridges and 2) noncycling dephosphorylated cross bridges ("latch bridges"). The major assumptions are that 1) Ca2+-dependent myosin phosphorylation is the only postulated regulatory mechanism, 2) each myosin head acts independently, and 3) latch bridges are formed by dephosphorylation of an attached cross bridge. Rate constants were resolved by fitting data on the time courses of myosin phosphorylation and stress development. Comparison of the rate constants indicates that latch-bridge detachment is the rate-limiting step. Model stimulations predicted a hyperbolic dependence of steady-state stress myosin phosphorylation, which corresponded with the experimental observation of high values of stress with low levels of phosphorylation in intact tissues. Model stimulations also predicted the experimental observation than an initial phosphorylation transient only accelerates stress development, with no effect on the final steady-state levels of stress. Because the only Ca2+-dependent regulatory mechanism in this model was activation of myosin light chain kinase, these results are consistent with the hypothesis that myosin phoshorylation is both necessary and sufficient for the development of the latch state.