EXERCISE TRAINING & THE MYOCARDIUM--CELLULAR ADAPTATIONS

描述：耐力运动训练有助于改善心脏 收缩功能，并使心脏更耐缺血 损伤 这些令人向往的中枢神经系统的细胞适应性 心脏适应性还没有被清楚地识别出来。 有证据 （大部分是间接的），改变心肌跨动脉膜Ca 2+处理可能 参与其中 此外，最近对完整LV心肌细胞的研究提供了 证据表明，训练增加了敏感性， Ca ~（2+）激活收缩元件（CE）。 这些问题将 使用跑步机运动训练的雌性大鼠模型， 实现以下具体目标。 具体目标1是直接 检测心肌NaCa交换活性 训练（TR）和久坐（SED）大鼠。 荧光显微镜（fura-2）， 全细胞电生理学和快速溶液转换技术将 用于确定训练是否影响电压和细胞内 [Ca2 NaCa交换电流（INaCa）和NaCa的+]-依赖性 （一）对培训的意见的交流介导解释 增加心脏对细胞外[Ca 2 +]的内向敏感性， [Na+]减少和（ii）导致心肌对 细胞外45 Ca ~（2+）。 具体目标二是 确定训练是否影响单个细胞中的复极化K+电流 使用全细胞电生理学技术。 时间依赖性（I10）和非时间依赖性（Is）K+电流密度， 将确定激活/失活特性。 的改变 这些电流，特别是Ito，可以影响心室动作电位， 构型，因此，跨动脉膜Ca 2+运动， 兴奋收缩 具体目标3是直接确定TR是否 影响收缩元件对Ca 2+激活的敏感性， 使用荧光的完整心肌细胞和小梁肌制备物 显微镜（Fura-2）、视频边缘检测和等距力转换。 这种类型的适应已经通过对肌细胞缩短的研究来推断， [Ca2+]动态，并可以提供一个替代的解释， 观察到训练增加了心脏的变力性敏感性 改变细胞外[Na+]和[Ca 2 +]（见具体目标1）。 信息 这个项目的成果将有助于我们了解 细胞过程，这些过程是心脏适应性的基础， 培训，并可能是有用的，在治疗的设计，可用于 心脏病的治疗和预防。

DESCRIPTION: Endurance exercise training elicits improved cardiac contractile function and renders the heart more resistant to ischemic injury. The cellular adaptations that underlie these desirable central cardiac adaptations have not been clearly identified. There is evidence (mostly indirect) that altered myocardial transarcolemmal Ca2+ handling may be involved. Additionally, recent studies of intact LV cardiocytes provide evidence consistent with the idea that training increases the sensitivity of the contractile element (CE) to activation by Ca2+. These issues will be addressed using a female rat model of treadmill exercise training to accomplish the following Specific Aims. Specific Aim 1 is to directly examine myocardial NaCa exchange activity in myocardium isolated from trained (TR) and sedentary (SED) rats. Fluorescence microscopy (fura-2), whole cell electrophysiology, and rapid solution switching techniques will be used to determine if training affects the voltage- and intracellular [Ca2+]-dependence of NaCa exchange currents (INaCa) and NaCa exchange-mediated explanations for the observations that training (i) increases the intropic sensitivity of the heart to extracellular [Ca2+] and [Na+] reduction and (ii) results in a smaller myocardial uptake of extracellular 45Ca2+ during bouts of ischemia. Specific Aim 2 is to determine if training influences repolarizing K+ currents in a single cardiocytes using whole cell electrophysiological techniques. Time-dependent (I10) and time-independent (Is) K+ current densities and activation/inactivation characteristics will be determined. Alterations in these currents, particularly Ito, could affect ventricular action potential configuration and, therefore, transarcolemmal Ca2+ movement during excitation-contraction. Specific Aim 3 is to directly determine if TR affects the sensitivity of the contractile element to activation by Ca2+ in intact cardiocytes and trabecular muscle preparations using fluorescence microscopy (fura-2), video edge detection, and isometric force transduction. This type of adaption has been inferred by studies of myocyte shortening and [Ca2+] dynamics and could provide an alternative explanation for the observation that training increases the inotropic sensitivity of the heart to altered extracellular [Na+] and [Ca2+] (see Specific Aim 1). Information resulting from this project will contribute to our understanding of the cellular processes that underlie the desirable adaptations of the heart to training and may be useful in the design of therapies that can be used in the treatment and prevention of heart disease.