ELECTROPHYSIOLOGY OF ADRENAL CORTICAL ENDOCRINE TISSUES

有三种主要的生理性的醛固酮促分泌剂作用于 肾上腺皮质球状带细胞：促肾上腺皮质激素、血管紧张素Ⅱ (所有)，和钾。细胞外钙离子是一种必需的 然而，最近的研究表明，每一种药物的激活都表明 每个案件的涉案地点都不同。暴露于隔离的 肾小球细胞对这三种物质浓度的升高 促分泌剂与膜去极化有关，但我们的 初步数据表明，发生这种情况的离子机制 每一种情况都是不同的。我们建议进行研究，以检查离子 分泌物的电生理相关机制和动力学 由这些药剂处理肾小球细胞而产生。实验 将在酶法分离的肾上腺细胞上进行 老鼠。这些研究将使用经典的电生理方法，如 以及最近发展起来的单电极电压钳技术 和膜片钳。 将解决以下试验性问题：(1)我们将 检查肾小球细胞的基本电生理特性。 具体地说，静止膜对Na+，K+，C1-的渗透率将为 以及K+和Ca++电导的电压依赖关系。 (2)我们将调查潜在的电生理事件 K+对激素分泌的调节作用。(3)我们会调查 伴随着细胞分泌调节的电生理事件 促分泌剂AII和ACTH以及那些潜在的 它们的拮抗剂(即多巴胺、心钠素等)穿着这些 细胞。 在正常人和正常血压大鼠中，限制钠和/或饮食 钾负荷均可提高肾小球细胞的反应性 到它的秘密会所。这种敏感性变化背后的机制 饮食摄入量的变化是未知的。我们将进行实验，以 看看这些敏感性变化的电生理相关性是否可以 在这些条件下表现出来的。近50%的患者患有必需的 高血压似乎缺乏这种钠介导的反应性变化。 敬所有人。一种遗传性高血压大鼠(SHR)具有类似的 反常现象。我们将对正常血压(Spraogue)进行比较研究 Dawley)和自发性高血压(SHR)大鼠 饮食中钠或钾摄入量的变化改变了基本的 肾小球细胞的电生理特性。

There are three major physiological aldosterone secretagogues which act on cells of the zona glomerulosa of the adrenal cortex: ACTH, angiotensin II (AII), and potassium. Extracellular calcium ion is a requirement for activation by each of these agents, however, recent studies suggest that the locus of its involvement differs for each case. Exposure of isolated glomerulosa cells to increased concentrations of all three of these secretagogues is associated with membrane depolarization, but our preliminary data demonstrate that the ionic mechanism by which this occurs in each case is different. We propose studies to examine the ionic mechanisms and kinetics of the electrophysiological correlates of secretion resulting from treatment of glomerulosa cells by these agents. Experiments will be performed on enzymatically isolated cells from adrenal glands of rats. These studies will employ classical electrophysiological methods as well as the recently developed techniques of single-electrode voltage clamp and patch clamp. The following experimental questions will be addressed: (1) We will examine the basal electrophysiological properties of glomerulosa cells. Specifically, the resting membrane permeabilities to Na+, K+, C1- will be examined as well as the voltage dependency of K+ and Ca++ conductances. (2) We will investigate the electrophysiological events underlying modulation of hormonal secretion by K+. (3) We will investigate the electrophysiological events accompanying modulation of secretion by the secretagogues AII and ACTH as well as those underlying the mechanisms of their antagonists (i.e. dopamine, atrial natriuretic factor, etc.) in these cells. In normal man and normotensive rats, sodium restriction and/or dietary potassium loading both increase the responsiveness of the glomerulosa cell to its secretagogues. The mechanisms underlying this change in sensitivity with changes in dietary intake are unknown. We will perform experiments to see if electrophysiological correlates of these sensitivity changes can be demonstrated under these conditions. Nearly 50% of patients with essential hypertension appear to lack this sodium mediated change in responsiveness to AII. A genetically hypertensive strain of rats (SHR) has a similar abnormality. We will perform comparative studies on normotensive (Sprague Dawley) and spontaneously hypertensive (SHR) rats designed to see if changes in dietary sodium or potassium intake modify the basic electrophysiological properties of the glomerulosa cell.