Dynamics of Oxygen Uptake in Contracting Single Myocytes

描述：（申请人提供）：骨骼肌的调整 氧化磷酸化反应更高的代谢率， 其特征在于延迟之后是单指数上升到稳定状态 在那里可以实现这一点。这种反应的设置部分是由于 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）O2按需输送，氧化还原和 磷酸化状态和增加的线粒体活化。虽然运动 训练可以加速V02动力学、疾病状态如心力衰竭， 糖尿病减慢VO2动力学。肌肉收缩的代谢反应是 部分由肌纤维类型组成决定，最近的数据表明， 一氧化氮（NO），一种参与运动充血的分子， 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），以阐明 肌纤维类型、NO和肌红蛋白的特定作用。具体而言是 关于从静止到静止的过渡，提出了以下假设： 电刺激收缩：1）缓慢氧化的肌细胞将具有 更快的VO2动力学，与较少氧化、较多糖酵解的纤维和 动力学的速度将与线粒体体积正相关 2）NO合酶的抑制将导致更快的VO2动力学， 相反，外源性NO将减慢VO2反应，和3）缺乏 肌红蛋白将显著减慢VO2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.