EXERCISE TRAINING & THE MYOCARDIUM--CELLULAR ADAPTATIONS

运动性心肌损伤的细胞机制 收缩性还不太清楚。 然而，似乎最好的 改善收缩功能的生化相关物包括 肌膜（SL）和肌浆网（SR）突起的改变 参与跨动脉膜和肌网状的调节 Ca 2+运动。 为了更好地了解功能 这些生化变化的意义，跑步机的影响 对细胞CA 2+流入的主要途径（“L”型）进行训练（TR Ca 2+通道）和外排（NaCa交换）将使用整体 细胞膜片钳技术在单个左心室（LV）心脏 肌细胞 (The将使用雌性大鼠模型、久坐（SED）和TR）。 (i)TR对“L”型电流（伊卡）和伊卡的影响 将测定失活动力学。 同样，电压-和 NaCa交换电流（INa/Ca）细胞内[Ca 2 +]依赖性将 接受检查。 这些研究是重要的，因为（1）伊卡集中在 参与调节SR的Ca 2+释放;（2）搏动间 由伊卡和INa/Ca实现的动态平衡在很大程度上定义了细胞的 SR Ca ~（2+）释放量与SR Ca ~（2+）含量成正比。 (ii)TR对SR Ca 2+含量的影响将使用快速 冷却挛缩（RCC）;相对（SED v TR）的影响 实验操作旨在差异干扰流入， 将检查RCC振幅上的流出机制。 碾压混凝土试验 将在单个LV肌细胞和小梁肌上进行 准备工作 (iii)TR对全球Ca 2+处理的影响 表现出高度天然细胞组织的制剂将 使用灌注的等容大鼠心脏制备物测定。 关于可释放的药物的动态调节的重要信息 SR Ca 2+可以通过检查心脏的收缩反应来导出 系统性地改变期前收缩和期前收缩后间期。 这些完整的器官数据对于我们理解 TR引起的细胞变化的重要性。 (iv)的 TR对收缩元件对以下的反应性的影响： 将使用透化的左心室小梁检查Ca 2+激活 显示肌节组织的肌肉标本。 运动训练 是一种独特的非病理生理应激源， 引起心肌中的生物化学和积极的功能变化。 培训在疾病预防和 康复活动. 该项目产生的信息将有助于 我们对心肌功能可塑性的理解， 可能对理解某些疾病的细胞病变很重要， 病理状态，以及改善这些病理状态的机制 病变

The cellular mechanisms underlying training-induced changes in myocardial contractility are not well understood. However, it appears that the best biochemical correlates of improved contractile function include alterations in sarcolemmal (SL) and sarcoplasmic reticular (SR) processes that are involved in the regulation of transarcolemmal and sarcoreticular Ca2+ movement. In order to gain a better understanding of the functional significance of these biochemical changes, the impact of treadmill training (TR) on the primary avenues of cellular CA2+ influx ("L" type Ca2+ channel) and efflux (NaCa exchange) will be examined using whole cell patch clamp techniques on single, left ventricular (LV) cardiac myocytes. (The female rat model, sedentary (SED) and TR, will be used). (i) The effect of TR on the magnitude of "L" type current (ICa) and ICa inactivation kinetics will be determined. Similarly, the voltage- and intracellular [Ca2+]-dependence of NaCa exchange current (INa/Ca) will be examined. These studies are important because (1) ICa is centrally involved in regulating Ca2+ release from the SR and (2) the beat-to-beat dynamic equilibrium achieved by ICa and INa/Ca largely defines cellular and SR Ca2+ content; SR Ca2+ release is proportional to SR Ca2+ content. (ii) The effect of TR on SR Ca2+ content will be examined using rapid cooling contractures (RCC); the relative (SED v TR) effects of experimental manipulations designed to differentially perturb influx and efflux mechanisms on RCC amplitude will be examined. RCC experiments will be performed on single LV myocytes and trebecular muscle preparations. (iii) The effect of TR on Ca2+ handling in a global preparation exhibiting a high degree of native cellular organization will be determined using a perfused, isovolumic rat heart preparation. Significant information regarding the dynamic regulation of releasable SR Ca2+ can be derived by examining the contractile response of the heart to systematically varied extrasystolic and post-extrasystolic intervals. These whole organ data will be critical in our understanding of the significance of the cellular changes that are produced by TR. (iv) The effect of TR on the responsiveness of the contractile element to activation by Ca2+ will be examined using a permeabilized LV trebecular muscle preparation exhibiting sarcomeric organization. Exercise training is a singularly unique nonpathophysiological stressor that is capable of eliciting biochemical and positive functional changes in the myocardium. Training can also be of significant value in disease prevention and rehabilitation. Information resulting from this project will contribute to our understanding of the functional plasticity of the myocardium and may be important in understanding the cellular lesions underlying certain pathological states, and the mechanisms involved in ameliorating those lesions.