Dynamics of Oxygen Uptake in Contracting Single Myocytes

描述：(申请人提供)：骨骼肌的调节 对较高代谢率的反应是氧化磷酸化 以延迟为特征的，随后以单指数上升到稳定状态 在那里可以实现这一点。设置此响应的部分原因是 复杂的无数事件，包括对流和传导的匹配 (通过肌红蛋白促进)02按需交付、氧化还原和 磷酸化状态，并增加线粒体的激活。在锻炼时 训练可以加速VO2动力学，心力衰竭等疾病状态和 糖尿病使V02动力学减慢。对肌肉收缩的代谢反应是 部分由肌肉纤维类型组成决定，最近的数据表明 一氧化氮(NO)，一种与运动性充血有关的分子，也会损害 线粒体功能。目前的建议旨在研究V02动力学在 分离的骨骼肌细胞(因此，与Q02问题无关)以阐明 肌肉纤维类型、一氧化氮和肌红蛋白的具体作用。具体地说， 关于从REST到REST的过渡，提出了以下假设 电刺激收缩：1)缓慢氧化的心肌细胞将 与氧化较少、糖酵解较多的纤维相比，V02动力学更快 动力学的速度将与线粒体体积呈正相关。 密度，2)抑制一氧化氮合酶将导致更快的V02动力学和 相反，外源性NO会减缓V02的反应，以及3)缺乏 肌红蛋白将显著减慢V02的动力学。

DESCRIPTION: (provided by applicant): The adjustment of skeletal muscle oxidative phosphorylation in response to higher metabolic rates is characterized by a delay followed by a monoexponential rise to steady state where this can be achieved. The setting of this response is due, in part, to a complex myriad of events including matching of convective, and conductive (facilitated via myoglobin) 02 delivery to demand, alterations in redox and phosphorylation state, and increased mitochondrial activation. While exercise training may speed V02 kinetics, disease states such as heart failure and diabetes slow V02 kinetics. Metabolic responses to muscle contractions are determined, in part, by muscle fiber type composition and recent data suggests that nitric oxide (NO), a molecule involved in exercise hyperemia, also impairs mitochondrial function. The present proposal aims to study V02 dynamics in isolated skeletal myocytes (thus, independent of Q02 issues) to elucidate specific roles of muscle fiber type, NO and myoglobin. Specifically, the following hypotheses are proposed regarding the transition from rest to electrically stimulated contraction: 1) Slow oxidative myocytes will have faster V02 kinetics compared with less oxidative, more glycolytic fibers and the speed of the kinetics will correlate positively with mitochondrial volume density, 2) Inhibition of NO synthase will result in faster V02 kinetics and conversely, exogenous NO will slow the V02 response, and 3) Absence of myoglobin will significantly slow V02 kinetics.