Fajmut Ales, Brumen Milan
Faculty of Natural Sciences and Mathematics, Medical Faculty, and Faculty of Health Sciences, University of Maribor, Slomskov trg 15, SI-2000 Maribor, Slovenia.
J Theor Biol. 2008 Jun 7;252(3):474-81. doi: 10.1016/j.jtbi.2007.10.005. Epub 2007 Oct 11.
In airway smooth muscles, kinase/phosphatase-dependent phosphorylation and dephosphorylation of the myosin light chain (MLC) have been revealed by many authors as important steps in calcium (Ca(2+)) signalling pathway from the variation of Ca(2+) concentration in cytosol to the force development. Here, a theoretical analysis of the control action of MLC-kinase (MLCK) and MLC-phosphatase (MLCP) in Ca(2+) signalling is presented and related to the general control principles of these enzymes, which were previously studied by Reinhart Heinrich and his co-workers. The kinetic scheme of the mathematical model considers interactions among Ca(2+), calmodulin (CaM) and MLCK and the well-known 4-state actomyosin latch bridge model, whereby a link between them is accomplished by the conservation relation of all species of MLCK. The mathematical model predicts the magnitude and velocity of isometric force in smooth muscles upon transient biphasic Ca(2+) signal. The properties of signal transduction in the system such as the signalling time, signal duration and signal amplitude, which are reflected in the properties of force developed, are studied by the principles of the metabolic control theory. The analysis of our model predictions confirms as shown by Reinhart Heinrich and his co-workers that MLCK controls the amplitude of signal more than its duration, whereas MLCP controls both. Finally, the simulations of elevated total content of MLCK, a typical feature of bronchial muscles of asthmatic subjects and spontaneously hypertensive rats as well as potentiation of MLCP catalytic activity, are carried out and are discussed in view of an increase in the force magnitude.
在气道平滑肌中，许多作者已揭示肌球蛋白轻链（MLC）的激酶/磷酸酶依赖性磷酸化和去磷酸化是钙（Ca(2+)）信号通路中从胞质溶胶中Ca(2+)浓度变化到力量产生的重要步骤。在此，我们对MLC激酶（MLCK）和MLC磷酸酶（MLCP）在Ca(2+)信号传导中的控制作用进行了理论分析，并将其与这些酶的一般控制原理相关联，这些原理先前由莱因哈特·海因里希及其同事进行过研究。数学模型的动力学方案考虑了Ca(2+)、钙调蛋白（CaM）和MLCK之间的相互作用以及著名的四态肌动球蛋白闩锁桥模型，通过MLCK所有物种的守恒关系在它们之间建立联系。该数学模型预测了平滑肌在瞬时双相Ca(2+)信号作用下等长力的大小和速度。利用代谢控制理论原理研究了系统中信号转导的特性，如信号时间、信号持续时间和信号幅度，这些特性反映在产生的力量特性中。正如莱因哈特·海因里希及其同事所示，我们对模型预测的分析证实，MLCK对信号幅度的控制大于对信号持续时间的控制，而MLCP对两者都有控制作用。最后，针对哮喘患者和自发性高血压大鼠支气管肌肉的典型特征——MLCK总含量升高以及MLCP催化活性增强进行了模拟，并从力量大小增加的角度进行了讨论。
