IONIC CURRENTS AND AUTONOMIC REGULATION IN HEART FAILURE

心力衰竭中的离子电流和自主调节

• 批准号: 6185043
• 负责人: ATSUKO YATANI
• 金额: $ 20.15万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185043
• 关键词: G protein; beta adrenergic receptor; calcium channel; calcium flux; cardiac myocytes; cellular pathology; electrophysiology; genetically modified animals; heart contraction; heart enlargement; heart failure; laboratory mouse; membrane potentials; membrane transport proteins; sodium potassium exchanging ATPase; voltage /patch clamp

Cardiac hypertrophy is an initial adaptive process in response to a variety of physiological and pathological stimuli. In certain conditions such as chronic hypertension, compensated hypertrophy an lead to congestive heart failure. Previous studies have proposed that abnormal excitation contraction coupling and regulation may be responsible for impaired contractility in failing heart. A number of Ca/2+ handling systems involved in myocardial contraction and the cellular basis for the defect in heart failure is not completely understood. In addition, the correlation between the functional abnormalities and the stages of hypertrophy, including before and during the onset of heart failure, as well as end stage congestive heart failure, has not been well- characterized. Our long term objective is to understand the cellular mechanisms that rigger cardiac hypertrophy and regulate the transition between compensated and decompensated phases of cardiac hypertrophy. This application focuses on cellular mechanisms important for myocardial Ca/2+ homeostasis . We hypothesize that changes in ionic currents and autonomic regulation that are involved in cellular Ca/2+ homeostasis occur in hypertrophied myocardium and that the degree of alteration is dependent upon the severity of hypertrophy and the presence of heart failure. To test this hypothesis, a transgenic mouse model of compensated hypertrophy which exhibits cardiac physiological events observed in animal models and human heart failure with a remarkable recapitulation with biochemical alterations associated with various stages of disease will be determined by patch clamp technique. Once the failure by transferring gene of certain defective components. This research is fundamental to our understanding of cellular mechanisms of cardiac hypertrophy and failure. These studies will not only field significant new information on the basic cellular mechanisms that regulate heart failure, but will also provide new and valuable insights into the design of drugs as well as novel therapeutic approaches for cardiovascular disease.

心脏肥大是对A的初始自适应过程 多种生理和病理刺激。在某些情况下 例如慢性高血压，补偿肥大的导致 充血性心力衰竭。先前的研究提出异常 激发收缩耦合和调节可能是负责的 心脏失败的收缩性受损。许多CA/2+处理 涉及心肌收缩的系统和细胞基础 心力衰竭缺陷尚未完全理解。此外， 功能异常与阶段之间的相关性 肥大，包括心力衰竭发作之前和期间 以及末期舞台充血性心力衰竭，还没有很好 特征。 我们的长期目标是了解细胞机制 索具心脏肥大并调节 心脏肥大的补偿和代偿阶段。这 应用侧重于对心肌重要的细胞机制 CA/2+稳态。我们假设离子电流的变化和 涉及细胞CA/2+稳态的自主法规 发生在肥大的心肌中，改变程度为 取决于肥大的严重程度和心脏的存在 失败。 为了检验这一假设，是补偿的转基因小鼠模型 肥大，表现出在 动物模型和人类心力衰竭，具有显着的概括 与疾病的各个阶段有关的生化改变 将通过斑块夹技术确定。一旦失败 转移某些缺陷成分的基因。 这项研究是我们对细胞机制的理解至关重要的 心脏肥大和衰竭。这些研究不仅会在 有关基本细胞机制的重要新信息 调节心力衰竭，但还将提供新的和有价值的见解 进入药物的设计以及新颖的治疗方法 心血管疾病。