Baudet S, Kuznetsov A, Merciai N, Gorza L, Ventura-Clapier R
URA CNRS 1340, Laboratoire de Cardiologie Expérimentale, Hôpital Laënnec, Nantes, France.
J Mol Cell Cardiol. 1994 Dec;26(12):1573-86. doi: 10.1006/jmcc.1994.1177.
Ferret right ventricular hypertrophy is characterized by a decreased and prolonged isometric contraction, associated with altered intracellular calcium (Ca2+) regulation. However myofibrillar composition, cross-bridge function and/or energy transfer may also be involved in these contractile disturbances. Therefore, mechanical properties of myofibrils have been studied with Triton X-100-skinned fibres and troponin (Tn) T and I composition has been examined. Mitochondrial function and functional activity of creatine kinase (CK) isoforms have been studied in saponin-skinned fibres of control (C) and hypertrophied (H) ferret right ventricle, to check for a possible mismatch between energy production and utilization. Our results show that neither TnT nor TnI isoform expression, nor myofibrillar Ca2+ responsiveness (similar apparent Ca2+ sensitivity and Hill coefficient) were affected by pressure-overload. Similarly, maximal tension and stiffness, as well as cross-bridge cycling rate (v)--assessed by quick length changes--were not significantly altered. Importantly, passive stiffness was dramatically increased (163 +/- 30 mN/mm2/microns for C v 500 +/- 121 mN/mm2/microns for H; P < 0.02). Moreover, there was a significant correlation between passive stiffness and cross-bridge cycling rate, indicating that a factor involved in the passive stiffness may affect cross-bridge kinetics. Oxidative capacity (normalized to ventricular dry weight), reflecting mitochondrial ATP production and mitochondrial CK efficacy, as well as myofibrillar CK efficacy (assessed by the shift of MgATP-rigor tension curves before and after phosphocreatine addition), were similar in both groups. These results demonstrate that ferret right ventricular pressure-overload was accompanied by a development of myofibrils and a parallel increase of energy production capacity, transfer and utilization. Decreased compliance, probably linked to an increase in the collagen fraction and/or alterations of the cytoskeletal architecture of the overloaded ventricle, could contribute to the slower time course and decreased amplitude of the isometric twitch.
雪貂右心室肥大的特征是等长收缩减弱且延长，这与细胞内钙（Ca2+）调节改变有关。然而，肌原纤维组成、横桥功能和/或能量传递也可能参与这些收缩紊乱。因此，已使用Triton X-100透皮纤维研究了肌原纤维的力学性能，并检测了肌钙蛋白（Tn）T和I的组成。已在对照（C）和肥大（H）雪貂右心室的皂角苷透皮纤维中研究了线粒体功能和肌酸激酶（CK）同工酶的功能活性，以检查能量产生与利用之间是否可能存在不匹配。我们的结果表明，压力超负荷并未影响TnT或TnI同工型表达，也未影响肌原纤维Ca2+反应性（相似的表观Ca2+敏感性和希尔系数）。同样，通过快速长度变化评估的最大张力和刚度以及横桥循环速率（v）也没有明显改变。重要的是，被动刚度显著增加（C组为163±30 mN/mm2/μm，H组为500±121 mN/mm2/μm；P<0.02）。此外，被动刚度与横桥循环速率之间存在显著相关性，表明参与被动刚度的一个因素可能影响横桥动力学。两组的氧化能力（以心室干重标准化）反映线粒体ATP产生和线粒体CK功效，以及肌原纤维CK功效（通过添加磷酸肌酸前后MgATP-强直张力曲线的变化评估）相似。这些结果表明，雪貂右心室压力超负荷伴随着肌原纤维的发育以及能量产生能力、传递和利用的平行增加。顺应性降低可能与胶原分数增加和/或超负荷心室细胞骨架结构改变有关，这可能导致等长收缩的时程变慢和幅度减小。
