NA+/K+ ATPASE AND CARDIAC PHYSIOLOGY

NA /K ATP酶和心脏生理学

• 批准号: 2520497
• 负责人: PAUL F JAMES
• 金额: $ 3.02万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-17 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2520497
• 关键词: calcium flux; calcium indicator; gene targeting; genetically modified animals; heart contraction; heart function; isozymes; laboratory mouse; ouabain; protein structure function; sodium potassium exchanging ATPase; tissue /cell culture

The overall goal of this research is to determine the function of the individual alpha subunit isoforms of the Na,K-ATPase and the role each plays in cardiac physiology. The Na,K-ATPase utilizes the energy derived from ATP hydrolysis to catalyze the transport of 3 Na+ ions out of the cell and 2 K+ ions into the cell. This enzyme produces electrical and chemical gradients which are necessary for a variety of cellular/physiological functions including the excitability of nerves and muscles and the restoration of calcium levels after cardiac muscle contraction. The Na,K-ATPase is a heteromeric enzyme composed of an alpha and a beta subunit. The alpha subunit, of which four isoforms exist, contains both the catalytic activity and is the receptor for cardiac glycosides. The cardiac glycoside class of compounds bind to and inhibit the Na,K-ATPase and are used in the treatment of congestive heart failure. Using genetic modulation of the Na,K-ATPase alpha isoforms, in knock-out and transgenic mice, we hope to identify specific functional roles for individual isoforms, better define the pharmacological aspects of cardiac glycoside therapy and provide a more detailed understanding of Na,K-ATPase inhibition as it relates to cardiac physiology.

本研究的总体目标是确定 Na，K-ATP酶的单个α亚基亚型和每个亚型的作用 在心脏生理学中起着重要作用。 Na，K-ATPase利用能量 来自ATP水解，催化3个Na+离子的运输 和2个K+离子进入细胞。 这种酶产生 电和化学梯度，这是必要的各种 细胞/生理功能，包括神经的兴奋性 和肌肉和恢复钙水平后，心肌 收缩。Na，K-ATP酶是一种异聚体酶， α和β亚基。 α亚基，其中四种亚型 存在，包含催化活性，是受体， 强心苷 强心苷类化合物结合到 并抑制Na，K-ATP酶，用于治疗充血性 心衰 利用Na，K-ATP酶α的遗传调节 同种型，在敲除和转基因小鼠中，我们希望鉴定出特异性的 单个亚型的功能作用，更好地定义 强心苷治疗的药理学方面，并提供了一个更 详细了解Na，K-ATP酶抑制，因为它涉及 心脏生理学