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.

心脏肥大是响应于心脏肥大的初始适应过程。 各种生理和病理刺激。在某些条件下 例如慢性高血压、代偿性肥大等 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造成 心脏衰竭时收缩力受损。一些Ca/2+处理 参与心肌收缩的系统和细胞基础 心力衰竭的缺陷尚不完全清楚。此外， 功能异常与阶段之间的相关性 肥厚，包括心力衰竭发作之前和期间，如 以及末期充血性心力衰竭，情况一直不好- 特点。 我们的长期目标是了解细胞机制 操纵者心脏肥大并调节之间的过渡 心脏肥大的代偿期和失代偿期。这 应用重点关注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 参与细胞 Ca/2+ 稳态的自主调节 发生在肥厚的心肌中，并且改变的程度是 取决于肥厚的严重程度和心脏的存在 失败。 为了验证这一假设，建立了补偿性转基因小鼠模型 肥大，表现出观察到的心脏生理事件 动物模型和人类心力衰竭的显着再现 与疾病各个阶段相关的生化改变 将通过膜片钳技术来确定。一旦失败由 转移某些缺陷成分的基因。 这项研究对于我们理解细胞机制至关重要 心脏肥大和衰竭。这些研究不仅将领域 关于基本细胞机制的重要新信息 调节心力衰竭，但也将提供新的和有价值的见解 药物设计以及新的治疗方法 心血管疾病。