Ohnuki Yoshiki, Nishimura Satoshi, Sugiura Seiryo, Saeki Yasutake
Department of Physiology, Tsurumi University School of Dental Medicine, Tsurumi-ku, Yokohama, Japan.
J Physiol Sci. 2008 Feb;58(1):15-20. doi: 10.2170/physiolsci.RP012807. Epub 2008 Jan 8.
To understand the pathophysiology of hereditary cardiomyopathy, we measured the phosphorylation status of regulatory proteins, troponin I (TnI), troponin T (TnT), myosin light chain 2 (MLC2), and myosin-binding protein C (MyBP-C), and the Ca2+-dependence of tension development and ATPase activity in skinned right ventricular trabeculae obtained from cardiomyopathic (TO-2 strain, n = 8) and control (F1B strain, n = 8) hamsters. The Ca2+ sensitivities of tension development and ATPase activity (mean +/- SD) were significantly (P < 0.0001) higher in the TO-2 strain (pCa50 5.64 +/- 0.04 in tension and 5.65 +/- 0.04 in ATPase activity) than in the F1B strain (pCa50 5.48 +/- 0.03 in tension and 5.51 +/- 0.03 in ATPase activity). No significant differences in their maximum values were observed between TO-2 (40.8 +/- 7.4 mN/mm2 in tension and 0.52 +/- 0.15 micromol/l/s in ATP consumption) and F1B (42.3 +/- 8.5 mN/mm2 in tension and 0.58 +/- 0.41 micromol/l/s in ATP consumption) preparations, indicating that the tension cost (ATPase activity/tension development) in TO-2 was quite similar to that in F1B. The phosphorylation levels of MLC2 and TnI were significantly (P < 0.01) lower in TO-2 than in F1B. These results suggest that the increase in the Ca2+ sensitivities of tension development and the ATPase activity in TO-2 hearts result from the decreased basal level of TnI phosphorylation, and these features can be considered to produce the incomplete diastolic relaxation and partly improve the systolic function in TO-2 hearts.
为了解遗传性心肌病的病理生理学，我们测量了调节蛋白肌钙蛋白I（TnI）、肌钙蛋白T（TnT）、肌球蛋白轻链2（MLC2）和肌球蛋白结合蛋白C（MyBP-C）的磷酸化状态，以及从心肌病（TO-2品系，n = 8）和对照（F1B品系，n = 8）仓鼠获取的去表皮右心室小梁中张力发展和ATP酶活性的钙依赖性。TO-2品系中张力发展和ATP酶活性的钙敏感性（平均值±标准差）显著（P < 0.0001）高于F1B品系（张力的pCa50为5.64±0.04，ATP酶活性的pCa50为5.65±0.04），而F1B品系中张力的pCa50为5.48±0.03，ATP酶活性的pCa50为5.51±0.03。在TO-2（张力为40.8±7.4 mN/mm2，ATP消耗为0.52±0.15 μmol/l/s）和F1B（张力为42.3±8.5 mN/mm2，ATP消耗为0.58±0.41 μmol/l/s）制剂之间未观察到其最大值有显著差异，这表明TO-2中的张力成本（ATP酶活性/张力发展）与F1B中的相当相似。TO-2中MLC2和TnI的磷酸化水平显著（P < 0.01）低于F1B。这些结果表明，TO-2心脏中张力发展和ATP酶活性的钙敏感性增加是由于TnI磷酸化基础水平降低所致，并且这些特征可被认为导致了TO-2心脏舒张期不完全松弛，并部分改善了收缩功能。
