Department of Physiology and Center for Muscle Biology, University of Kentucky, Lexington, KY, USA.
Pflugers Arch. 2011 Jul;462(1):3-14. doi: 10.1007/s00424-011-0952-3. Epub 2011 Mar 16.
When cardiac myocytes are stretched by a longitudinal strain, they develop proportionally more active force at a given sub-maximal Ca(2+) concentration than they did at the shorter length. This is known as length-dependent activation. It is one of the most important contributors to the Frank-Starling relationship, a critical part of normal cardiovascular function. Despite intense research efforts, the mechanistic basis of the Frank-Starling relationship remains unclear. Potential mechanisms involving myofibrillar lattice spacing, titin-based effects, and cooperative activation have all been proposed. This review summarizes some of these mechanisms and discusses two additional potential theories that reflect the effects of localized strains that occur within and between half-sarcomeres. The main conclusion is that the Frank-Starling relationship is probably the integrated result of many interacting molecular mechanisms. Multiscale computational modeling may therefore provide the best way of determining the key processes that underlie length-dependent activation and their relative strengths.
当心肌细胞受到纵向应变时，它们在给定的亚最大 Ca(2+)浓度下比在较短长度时产生更大比例的主动力。这被称为长度依赖性激活。它是弗兰克-斯塔尔定律的最重要贡献者之一，是正常心血管功能的关键部分。尽管进行了大量研究，但弗兰克-斯塔尔定律的机制基础仍不清楚。涉及肌原纤维晶格间距、titin 基效应和协同激活的潜在机制都已被提出。本综述总结了其中的一些机制，并讨论了另外两个潜在的理论，这些理论反映了在半肌节内和之间发生的局部应变的影响。主要结论是，弗兰克-斯塔尔定律可能是许多相互作用的分子机制的综合结果。因此，多尺度计算建模可能是确定长度依赖性激活及其相对强度的关键过程的最佳方法。
