Troponin and titin coordinately regulate length-dependent activation in skinned porcine ventricular muscle

We investigated the molecular mechanism by which troponin (Tn) regulates the Frank-Starling mechanism of the heart. Quasi-complete reconstitution of thin filaments with rabbit fast skeletal Tn (sTn) attenuated length-dependent activation in skinned porcine left ventricular muscle, to a magnitude similar to that observed in rabbit fast skeletal muscle. The rate of force redevelopment increased upon sTn reconstitution at submaximal levels, coupled with an increase in Ca2+ sensitivity of force, suggesting the acceleration of cross-bridge formation and, accordingly, a reduction in the fraction of resting cross-bridges that can potentially produce additional active force. An increase in titin-based passive force, induced by manipulating the prehistory of stretch, enhanced length-dependent activation, in both control and sTn-reconstituted muscles. Furthermore, reconstitution of rabbit fast skeletal muscle with porcine left ventricular Tn enhanced length-dependent activation, accompanied by a decrease in Ca2+ sensitivity of force. These findings demonstrate that Tn plays an important role in the Frank-Starling mechanism of the heart via on-off switching of the thin filament state, in concert with titin-based regulation.

我们研究了肌钙蛋白（Tn）调节心脏的弗兰克 - 斯塔林机制的分子机制。用兔快肌骨骼肌肌钙蛋白（sTn）对细丝进行近乎完全的重组，减弱了去皮猪左心室肌中长度依赖性激活，其程度与在兔快肌骨骼肌中观察到的相似。在亚最大水平下，sTn重组时力的重新发展速率增加，同时力对Ca2 +的敏感性增加，这表明横桥形成加速，相应地，可能产生额外主动力的静息横桥比例降低。通过操纵拉伸的既往史诱导的基于肌联蛋白的被动力增加，在对照肌和sTn重组肌中都增强了长度依赖性激活。此外，用猪左心室肌钙蛋白对兔快肌骨骼肌进行重组增强了长度依赖性激活，同时力对Ca2 +的敏感性降低。这些发现表明，Tn通过细丝状态的开 - 关转换，与基于肌联蛋白的调节协同作用，在心脏的弗兰克 - 斯塔林机制中起重要作用。