Terui Takako, Sodnomtseren Munguntsetseg, Matsuba Douchi, Udaka Jun, Ishiwata Shin'ichi, Ohtsuki Iwao, Kurihara Satoshi, Fukuda Norio
Department of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
J Gen Physiol. 2008 Mar;131(3):275-83. doi: 10.1085/jgp.200709895.
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Frank-Starling机制的分子机制。用兔快肌肌钙蛋白（sTn）对细肌丝进行近乎完全的重组，减弱了去表皮猪左心室肌的长度依赖性激活，其程度与在兔快肌中观察到的相似。在次最大水平下，sTn重组后力的重新发展速率增加，同时力的Ca2+敏感性增加，这表明横桥形成加速，因此，可潜在产生额外主动力的静息横桥比例降低。通过操纵拉伸的预拉伸历史诱导的基于肌联蛋白的被动力增加，增强了对照和sTn重组肌肉中的长度依赖性激活。此外，用猪左心室Tn重组兔快肌增强了长度依赖性激活，同时力的Ca2+敏感性降低。这些发现表明，Tn通过细肌丝状态的开关切换，与基于肌联蛋白的调节协同作用，在心脏的Frank-Starling机制中起重要作用。
