Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.
J Physiol. 2010 Aug 1;588(Pt 15):2891-903. doi: 10.1113/jphysiol.2010.190504. Epub 2010 Jun 7.
According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length-tension relationships appear able to switch between slow-twitch-like and fast-twitch-like by PKA-mediated myofibrillar phosphorylation, which implicates a novel means for controlling Frank-Starling relationships.
根据弗兰克-斯塔林关系,心室容积的增加会增加心输出量,这有助于使心输出量与外周循环需求相匹配。这种关系的细胞基础在很大程度上是肌丝长度-张力关系。在最大钙激活的制剂中,长度-张力关系相对较浅,并且在心肌细胞和骨骼肌纤维之间相似。在抽搐激活过程中,长度-张力关系在心肌和骨骼肌中都变得更加陡峭;然而,在亚最大激活过程中,不同类型的横纹肌细胞之间的张力长度依赖性是否不同仍不清楚。本研究的目的是比较大鼠左心室心肌细胞和快肌和慢肌纤维的肌节长度-张力关系以及肌节长度对力发展的依赖性。肌肉细胞制剂被钙激活以产生 50%的最大力,之后在一系列肌节长度下测量等长力和力发展的速率常数(k(tr))。快肌纤维的肌丝长度-张力关系明显比慢肌纤维陡峭。有趣的是,心肌细胞制剂表现出两种肌节长度-张力关系,一种比快肌纤维陡峭,另一种与慢肌纤维相似。此外,通过蛋白激酶 A(PKA)诱导的肌丝磷酸化,具有浅肌节长度-张力关系的心肌细胞被转化为陡峭的肌节长度-张力关系。三种细胞类型之间的肌节长度-k(tr)关系明显不同,表现出与 Ca(2+)激活依赖性 k(tr)关系明显不同的模式。总的来说,这些发现表明心肌细胞表现出不同的肌节长度-张力关系,肌节长度似乎是力发展速率的主要调节剂。重要的是,心肌细胞的肌节长度-张力关系似乎能够通过 PKA 介导的肌纤维磷酸化在慢肌样和快肌样之间切换,这暗示了一种控制弗兰克-斯塔林关系的新方法。