Dynamics of Oxygen Uptake in Contracting Single Myocytes

描述：（申请人提供）：骨骼肌的调整 响应较高代谢率的氧化磷酸化是 其特征是延迟后单指数上升到稳态 哪里可以实现这一点。该响应的设置部分归因于 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 满足需求、改变氧化还原和 磷酸化状态，并增加线粒体激活。运动时 训练可以加速 V02 动力学、心力衰竭等疾病状态和 糖尿病减慢 V02 动力学。对肌肉收缩的代谢反应是 部分取决于肌纤维类型组成，最近的数据表明 一氧化氮（NO）是一种参与运动充血的分子，也会损害 线粒体功能。本提案旨在研究 V02 动力学 分离的骨骼肌细胞（因此，独立于 Q02 问题）来阐明 肌纤维类型、NO 和肌红蛋白的具体作用。具体来说， 关于从休息到休息的转变，提出以下假设： 电刺激收缩：1）缓慢氧化的肌细胞会产生 与较少的氧化、更多的糖酵解纤维相比，更快的 V02 动力学 动力学速度与线粒体体积正相关 密度，2) 抑制 NO 合酶将导致更快的 V02 动力学和 相反，外源性 NO 会减慢 V02 反应，并且 3) 缺乏 肌红蛋白会显着减缓摄氧量动力学。

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.