NA+/K+ ATPASE AND CARDIAC PHYSIOLOGY

这项研究的总体目标是确定 Na，K-ATPase的各个α亚基异构体及其各自的作用 在心脏生理学方面发挥作用。Na，K-ATPase利用能量 从ATP水解中衍生出来催化3个Na+离子的运输 和2个K+离子进入细胞。这种酶能产生 电和化学梯度，这是各种 细胞/生理功能，包括神经的兴奋性 和肌肉与心肌后钙水平的恢复 收缩。Na，K-ATPase是一种异构酶，由一种 阿尔法亚基和贝塔亚基。α亚基，其中有四种亚型 存在，既包含催化活性，也是 强心苷。心脏糖苷类化合物结合于 和抑制Na，K-ATPase，并用于治疗充血性心力衰竭 心力衰竭。利用Na，K-ATPaseα的遗传调控 在基因敲除和转基因小鼠中，我们希望识别出特定的 单个异构体的功能角色，更好地定义 药理学方面的心脏糖苷治疗，并提供了更多 对Na，K-ATPase抑制的详细了解 心脏生理学。

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.