Solaro R J, Van Eyk J
Department of Physiology and Biophysics, College of Medicine, University of Illinois, Chicago 60612-7342, USA.
J Mol Cell Cardiol. 1996 Feb;28(2):217-30. doi: 10.1006/jmcc.1996.0021.
The transition of cardiac muscle myofilament activity from the diastolic to the systolic state is a complex allosteric/co-operative process, rich in potential control mechanisms. The rate and intensity of the transition is modulated by the mechanical state of the myofilaments, by covalent and non-covalent mechanisms, and by the isoform population of myofilament proteins. Moreover, the process is altered in pathological states and subject to modification by pharmacological agents with potential use as inotropic drugs. We present here a current perception of the process, with focus on molecular interactions of the thin filament components, especially troponin I. Our discussion is couched in terms of what we believe to be pressing questions in the current state of knowledge of this system. These questions are as follows: what is the topology of the thin filament and how do thin filament proteins regulate the activation of cross-bridge cycling? What is the relative role of protein phosphorylation of thin filament proteins in the regulation of the cardiac activity and dynamics? What is the relative role of feedback effects of cross-bridge binding on thin filament activity? Answers to these questions have taken on new significance, with the identification of familial hypertrophic cardiomyopathy as a "sarcomeric" disease related to missense mutations in myosin, troponin T. and tropomyosin. As discussed, new and exciting developments in this area are bringing us closer to the answers to these questions.
心肌肌丝活动从舒张状态向收缩状态的转变是一个复杂的别构/协同过程，具有丰富的潜在调控机制。这种转变的速率和强度受到肌丝的机械状态、共价和非共价机制以及肌丝蛋白同工型群体的调节。此外，该过程在病理状态下会发生改变，并可被具有潜在强心药物用途的药理试剂所修饰。我们在此呈现对该过程的当前认识，重点关注细肌丝成分的分子相互作用，尤其是肌钙蛋白I。我们的讨论围绕我们认为在该系统当前知识状态下亟待解决的问题展开。这些问题如下：细肌丝的拓扑结构是怎样的，细肌丝蛋白如何调节横桥循环的激活？细肌丝蛋白的磷酸化在心脏活动和动力学调节中的相对作用是什么？横桥结合对细肌丝活动的反馈作用的相对作用是什么？随着家族性肥厚型心肌病被确定为一种与肌球蛋白、肌钙蛋白T和原肌球蛋白错义突变相关的“肌节”疾病，这些问题的答案具有了新的意义。如所讨论的，该领域新的、令人兴奋的进展正使我们更接近这些问题的答案。
