Department of Clinical Neurophysiology, Uppsala University Hospital, Sweden.
Neuromuscul Disord. 2010 Feb;20(2):98-101. doi: 10.1016/j.nmd.2009.11.010. Epub 2009 Dec 16.
Ca(2+) ions are key regulators of skeletal muscle contraction. By binding to contractile proteins, they initiate a cascade of molecular events leading to cross-bridge formation and ultimately, muscle shortening and force production. The ability of contractile proteins to respond to Ca(2+) attachment, also known as Ca(2+) sensitivity, is often compromised in acquired and congenital skeletal muscle disorders. It constitutes, undoubtedly, a major physiological cause of weakness for patients. In this review, we discuss recent studies giving strong molecular and cellular evidence that pharmacological modulators of some of the contractile proteins, also termed Ca(2+) sensitizers, are efficient agents to improve Ca(2+) sensitivity and function in diseased skeletal muscle cells. In fact, they compensate for the impaired contractile proteins response to Ca(2+) binding. Currently, such Ca(2+) sensitizing compounds are successfully used for reducing problems in cardiac disorders. Therefore, in the future, under certain conditions, these agents may represent an emerging class of agents to enhance the quality of life of patients suffering from skeletal muscle weakness.
钙离子是骨骼肌肉收缩的关键调节因子。通过与收缩蛋白结合，它们引发一系列分子事件，导致横桥形成，最终导致肌肉缩短和力量产生。收缩蛋白对 Ca(2+)附着的反应能力，也称为 Ca(2+)敏感性，在获得性和先天性骨骼肌肉疾病中经常受到损害。这无疑是患者无力的主要生理原因。在这篇综述中，我们讨论了最近的研究，这些研究提供了强有力的分子和细胞证据，表明一些收缩蛋白的药理学调节剂，也称为 Ca(2+)敏化剂，是有效提高患病骨骼肌细胞 Ca(2+)敏感性和功能的药物。事实上，它们补偿了收缩蛋白对 Ca(2+)结合的反应受损。目前，这些 Ca(2+)敏化化合物已成功用于减少心脏疾病中的问题。因此，在未来的某些情况下，这些药物可能代表一类新兴的药物，可以提高患有肌肉无力的患者的生活质量。
