EXERCISE TRAINING & THE MYOCARDIUM--CELLULAR ADAPTATIONS

运动诱导心肌细胞变化的细胞机制 收缩能力还没有被很好地理解。然而，看起来最好的 改善收缩功能的生化相关因素包括 肌膜(SL)和肌浆网(SR)突的改变 参与跨关节膜和肌网的调节 CA2运动。为了更好地了解功能 这些生化变化的意义，对跑步机的影响 关于细胞内钙离子内流的主要途径的训练(“L”型) CA2通道)和外流(NACA交换)将使用 细胞膜片钳技术在单个左心室(LV)心脏的应用 肌细胞。(将使用雌性大鼠模型，静坐(SED)和TR)。 (I)tR对“L”型电流(ICa)和ICa幅度的影响 将确定失活动力学。同样，电压-和 细胞内[钙]-依赖的NACA交换电流(Ina/Ca)将 接受检查。这些研究很重要，因为(1)ICA是中枢 参与调节SR的钙释放，以及(2)节拍 ICA和Ina/Ca实现的动态平衡在很大程度上定义了细胞 和肌质网钙含量，肌质网钙释放与肌质网钙含量成正比。 (Ii)使用RAPID技术检测TR对SR钙含量的影响 冷却收缩(RCC)；相对(SED V Tr)效应 实验操作被设计成不同地扰动流入和 我们将研究RCC幅度的外流机制。碾压混凝土试验 将在单个左心室肌细胞和小梁肌肉上进行 准备工作。(Iii)tr在全球范围内对钙处理的影响 表现出高度天然细胞组织的准备工作将 用灌流等容大鼠心脏制剂测定。 关于可发布的动态监管的重要信息 可通过检查心脏的收缩反应得出肌浆网钙。 系统地改变早搏和早搏后间期。 这些完整的器官数据将对我们理解 由tr产生的细胞变化的意义。(Iv) 去甲肾上腺素对收缩元件反应性的影响 钙离子的激活将使用渗透性左心室小梁进行检测 肌肉准备显示肌节组织的肌肉准备。运动训练 是一种独特的非病理生理学应激源，能够 引起心肌生化和正功能改变。 培训在疾病预防和培训方面也具有重要价值 康复。这个项目产生的信息将有助于 对于我们对心肌和心肌的功能可塑性的理解 对于理解某些特定的细胞损伤可能很重要 病理状态，以及改善这些状态的机制 损伤。

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.