REGULATION OF NA/K PUMP FUNCTION

这个研究项目的长期目标是了解Na/K如何 泵：1)在生理上调节其活动，对 2)受病理生理调节； 3)参与调节维持离子的重要作用 可兴奋细胞表面膜的梯度及其在细胞中的作用 治疗药物(即强心苷)的作用部位。它是 同样变得明显的是，正常的心脏活动和一些病理 状态(如缺血、低钾和低镁血症)改变Na/K泵 功能和/或对糖苷类药物的敏感性。 该项目将研究从鸡胚胎中分离的心肌细胞， 膜片钳技术联合应用于大鼠和豚鼠 选择使用微量荧光分光光度法。因为文献中包含了 钠钾泵功能和糖苷敏感性差异较大的报道 对于每个物种和物种之间，3个物种的使用将提供 有价值的控制数据，将澄清这些明显的差异 Na/K泵功能的调节。拟议的实验协议将 提供有关1)调节Na/K泵功能的因素的新信息 (2)改变糖苷类药物敏感性。具体地说，钠、钾、钙的作用 和H离子(细胞内和细胞外)和心脏活性物质(例如， 神经递质)对Na/K泵的影响。此外，Na/K泵是如何 心肌的功能可能适应病理生理状态(例如 低钾血症)将在旨在测量Na/K的实验中进行研究 泵在已按惯例改变的制剂中的功能(例如 在低钾条件下生长)。这些实验将提供新的信息 Na/K泵功能的病理生理学。

The long range goal of this research project is to understand how the Na/K pump: 1) is physiologically regulated in its activity, sensitivity to cardiac glycosides and site density; 2) is regulated pathophysiologically; and 3) is involved in the regulation of important role in maintaining ion gradients across the surface membrane of excitable cells and its role as the site of action of therapeutic agents (i.e., cardiac glycosides). It is also becoming apparent that normal cardiac activity and some pathological states (e.g., ischemia, hypokalemia and hypomagnesemia) alter Na/K pump function and/or sensitivity to glycosides. This project will study isolated cardiac muscle cells from embryonic chick, rat and guinea pig with the patch clamp technique in conjunction with selected use of microspectrofluorometry. Since the literature contains reports on Na/K pump function and glycoside sensitivity which vary widely for each species and between species, the use of 3 species will provide valuable control data which will clarify these apparent differences in regulation of Na/K pump function. The proposed experimental protocols will provide new information about factors which 1) regulate Na/K pump function and 2) alter glycoside sensitivity. Specifically, the actions of Na, K, Ca and H ions (both intra- and extra-cellular) and cardioactive agents (e.g., neurotransmitters) on Na/K pump studied. Furthermore, how Na/K pump function in cardiac muscle might adapt to pathophysiological states (e.g. hypokalemia) will be investigated in experiments designed to measure Na/K pump function in preparations which have been cronically altered (e.g. growth in low K medium). These experiments will provide new information on the pathophysiology of Na/K pump function.