Hai C M, Murphy R A
Department of Physiology, School of Medicine, University of Virginia, Charlottesville 22908.
Am J Physiol. 1988 Jan;254(1 Pt 1):C99-106. doi: 10.1152/ajpcell.1988.254.1.C99.
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 simulations predicted a hyperbolic dependence of steady-state stress on myosin phosphorylation, which corresponded with the experimental observation of high values of stress with low levels of phosphorylation in intact tissues. Model simulations also predicted the experimental observation that 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 phosphorylation is both necessary and sufficient for the development of the latch state.
我们已经开发了一个用于平滑肌中横桥与细肌丝相互作用的最小动力学模型。该模型假设存在两种类型的横桥相互作用：1）循环磷酸化横桥和2）非循环去磷酸化横桥（“闭锁桥”）。主要假设为：1）钙依赖性肌球蛋白磷酸化是唯一假定的调节机制；2）每个肌球蛋白头部独立起作用；3）闭锁桥由附着的横桥去磷酸化形成。通过拟合肌球蛋白磷酸化和应力发展时间进程的数据来解析速率常数。速率常数的比较表明，闭锁桥脱离是限速步骤。模型模拟预测稳态应力对肌球蛋白磷酸化呈双曲线依赖性，这与完整组织中低磷酸化水平下高应力值的实验观察结果相符。模型模拟还预测了实验观察结果，即初始磷酸化瞬变仅加速应力发展，而对最终稳态应力水平无影响。由于该模型中唯一的钙依赖性调节机制是肌球蛋白轻链激酶的激活，这些结果与肌球蛋白磷酸化对于闭锁状态的发展既必要又充分这一假设一致。
