Stelzer Julian E, Larsson Lars, Fitzsimons Daniel P, Moss Richard L
Department of Physiology, University of Wisconsin Medical School, Madison, WI 53706, USA.
J Gen Physiol. 2006 Feb;127(2):95-107. doi: 10.1085/jgp.200509432.
Recent evidence suggests that ventricular ejection is partly powered by a delayed development of force, i.e., stretch activation, in regions of the ventricular wall due to stretch resulting from torsional twist of the ventricle around the apex-to-base axis. Given the potential importance of stretch activation in cardiac function, we characterized the stretch activation response and its Ca2+ dependence in murine skinned myocardium at 22 degrees C in solutions of varying Ca2+ concentrations. Stretch activation was induced by suddenly imposing a stretch of 0.5-2.5% of initial length to the isometrically contracting muscle and then holding the muscle at the new length. The force response to stretch was multiphasic: force initially increased in proportion to the amount of stretch, reached a peak, and then declined to a minimum before redeveloping to a new steady level. This last phase of the response is the delayed force characteristic of myocardial stretch activation and is presumably due to increased attachment of cross-bridges as a consequence of stretch. The amplitude and rate of stretch activation varied with Ca2+ concentration and more specifically with the level of isometric force prior to the stretch. Since myocardial force is regulated both by Ca2+ binding to troponin-C and cross-bridge binding to thin filaments, we explored the role of cross-bridge binding in the stretch activation response using NEM-S1, a strong-binding, non-force-generating derivative of myosin subfragment 1. NEM-S1 treatment at submaximal Ca2+-activated isometric forces significantly accelerated the rate of the stretch activation response and reduced its amplitude. These data show that the rate and amplitude of myocardial stretch activation vary with the level of activation and that stretch activation involves cooperative binding of cross-bridges to the thin filament. Such a mechanism would contribute to increased systolic ejection in response to increased delivery of activator Ca2+ during excitation-contraction coupling.
最近的证据表明，心室射血部分是由心室壁区域因心室围绕心尖 - 心底轴扭转产生的拉伸而导致的力延迟发展（即拉伸激活）提供动力的。鉴于拉伸激活在心脏功能中的潜在重要性，我们在22摄氏度下，于不同钙离子浓度的溶液中，对小鼠去垢剂处理的心肌的拉伸激活反应及其对钙离子的依赖性进行了表征。通过突然对等长收缩的肌肉施加初始长度0.5 - 2.5%的拉伸，然后将肌肉保持在新长度来诱导拉伸激活。对拉伸的力反应是多相的：力最初与拉伸量成比例增加，达到峰值，然后下降到最小值，之后再发展到新的稳定水平。反应的最后这个阶段是心肌拉伸激活的延迟力特性，推测是由于拉伸导致横桥附着增加。拉伸激活的幅度和速率随钙离子浓度变化，更具体地说，随拉伸前的等长力水平变化。由于心肌力既受钙离子与肌钙蛋白 - C结合的调节，也受横桥与细肌丝结合的调节，我们使用NEM - S1（肌球蛋白亚片段1的一种强结合、不产生力的衍生物）探讨了横桥结合在拉伸激活反应中的作用。在次最大钙离子激活的等长力下进行NEM - S1处理，显著加速了拉伸激活反应的速率并降低了其幅度。这些数据表明，心肌拉伸激活的速率和幅度随激活水平变化，并且拉伸激活涉及横桥与细肌丝的协同结合。这样一种机制将有助于在兴奋 - 收缩偶联期间，随着激活钙离子递送增加而使收缩期射血增加。
