Exercise Training & the Myocardium--Cellular Adaptations

描述（申请人摘要）：众所周知，耐力运动 训练在心肌性能方面产生一致有利的适应。 众所周知，训练可以改变心室动作的结构 电位（AP）和心脏对 细胞外Ca ~（2+）和Na ~+。然而，到目前为止，这些细胞的基础 适应尚未明确。在上一个融资期， 项目，我们已经确定了培训适应在这两个瞬态（伊藤） 和复合物的持续（Is）成分，外向复极化K+电流 在大鼠左心室（LV）心肌细胞中。这些复极化的钾离子电流 在定义AP配置中起核心作用，并且很可能是蜂窝基础 训练对AP特征的影响。最近，复合伊藤和 伊藤电流已被分解为至少4个其他离散外向 水流此外，这些离散电流和K+通道中的一些 据认为，负责这些电流的蛋白质是已知的， 差异分布在LV的特定区域。在这个项目中， 具体目标1是确定训练对特定电流的影响 在大鼠左心室中，使用全 细胞电生理技术具体目标2是确定是否 或不训练对特定电流的影响， 复合瞬态和持续电流区域分布在 心最后，我们最近获得了有趣的初步证据， 轻微的训练引起细胞内Ca 2+缓冲能力的降低。这 一种适应类型可以为这种共识提供细胞解释 观察到训练改变了心脏的变力性反应， 细胞外Ca ~（2+）和Na ~+的变化。具体目标3是使用 电生理技术和更精细的荧光显微镜 技术来证实或反驳这一潜在的重要发现。行使 众所周知，培训在预防和治疗广泛的 各种心脏病理状况。阐明细胞变化， 这些积极适应的基础可能特别重要 分子和药理学心脏的设计、开发和实施 疾病治疗和预防战略。这一点特别重要 鉴于心脏病夺去了更多的北美人的生命， 任何其他疾病。

DESCRIPTION (Applicant's abstract): It is well known that endurance exercise training elicits uniformly favorable adaptations in myocardial performance. Training is known to alter the configuration of the ventricular action potential (AP) and the inotropic responsiveness of heart to changes in extracellular (Ca2+) and (Na+). To date, however, the cellular basis for these adaptations has not been clearly identified. In the last funding period of this project, we have identified training adaptations in both the transient (Ito) and sustained (Is) components of the composite, outward repolarizing K+ current in rat left ventricular (LV) cardiocytes. These repolarizing K+ currents play a central role in defining AP configuration, and may well be the cellular basis for the effect of training on AP characteristics. Recently, composite Ito and Ito currents have been resolved into at least 4 other discrete outward currents. In addition, some of these discrete currents and the K+ channel proteins that are thought to be responsible for those currents are known to be differentially distributed across specific regions of the LV. In this project, Specific Aim 1 is to determine the effect of training on the specific current components that contribute to the composite Ito and Isus in rat LV using whole cell, electrophysiological techniques. Specific Aim 2 is to determine whether or not the effects of training on the specific currents that contribute to the composite transient and sustained currents are regionally distributed in the heart. Finally, we recently acquired intriguing preliminary evidence for a subtle training-induced decrease in intracellular Ca2+ buffering capacity. This type of adaptation could provide a cellular explanation for the consensus observation that training alters the inotropic responsiveness of heart to changes in extracellular (Ca2+) and (Na+). Specific Aim 3 is to use electrophysiological techniques and more refined fluorescence microscopic techniques to confirm or refute this potentially important finding. Exercise training is known to be effective in the prevention and treatment of wide variety cardio pathologic conditions. Elucidation of the cellular changes that underlie these positive adaptations may be of particular importance in the design, development, and implementation of molecular and pharmacological heart disease treatment and prevention strategies. This is particularly significant in view of the fact that heart disease claims more North American lives than any other disease.