Mikane T, Araki J, Kohno K, Nakayama Y, Suzuki S, Shimizu J, Matsubara H, Hirakawa M, Takaki M, Suga H
Department of Physiology II, Okayama University Medical School, Japan.
Am J Physiol. 1997 Dec;273(6):H2891-8. doi: 10.1152/ajpheart.1997.273.6.H2891.
We have reported that, in canine hearts, cardiac cooling to 29 degrees C enhanced left ventricular contractility but changed neither the contractile efficiency of cross-bridge (CB) cycling nor the excitation-contraction coupling energy. The mechanism of this intriguing energetics remained unknown. To get insights into this mechanism, we simulated myocardial cooling mechanoenergetics using basic Ca2+ and CB kinetics. We assumed that both adenosinetriphosphatase (ATPase)-dependent sarcoplasmic reticulum (SR) Ca2+ uptake and CB detachment decelerated with cooling. We also assumed that all the ATPase-independent SR Ca2+ release, Ca2+ binding to and dissociation from troponin, and CB attachment remained unchanged. The simulated cooling shifted the CB force-free Ca2+ concentration curve to a lower Ca2+ concentration, increasing the Ca2+ responsiveness of CB force generation, and increased the maximum Ca(2+)-activated force. The simulation most importantly showed that these cooling effects combined led to a constant contractile efficiency when Ca2+ uptake and CB detachment rate constants changed appropriately. This result seems to account for our experimentally observed constant contractile efficiency under cooling inotropy.
我们曾报道，在犬类心脏中，将心脏冷却至29摄氏度可增强左心室收缩力，但既不改变横桥（CB）循环的收缩效率，也不改变兴奋 - 收缩偶联能量。这种有趣的能量学机制仍然未知。为了深入了解这一机制，我们使用基本的Ca2+和CB动力学模拟了心肌冷却的机械能量学。我们假设依赖三磷酸腺苷酶（ATPase）的肌浆网（SR）Ca2+摄取和CB解离都会随着冷却而减速。我们还假设所有不依赖ATPase的SR Ca2+释放、Ca2+与肌钙蛋白的结合和解离以及CB附着均保持不变。模拟的冷却使CB无负荷Ca2+浓度曲线向较低的Ca2+浓度移动，增加了CB产生力时对Ca2+的反应性，并增加了最大Ca(2+)激活力。最重要的是，模拟结果表明，当Ca2+摄取和CB解离速率常数适当改变时，这些冷却效应共同导致收缩效率恒定。这一结果似乎解释了我们在冷却性变力作用下实验观察到的恒定收缩效率。
