ELECTROPHYSIOLOGY OF ADRENAL CORTICAL ENDOCRINE TISSUES

有三种主要的生理性醛固酮促分泌素， 肾上腺皮质肾小球细胞：ACTH、血管紧张素II (AII)和钾。 细胞外钙离子是一个必要条件， 然而，最近的研究表明， 其参与的场所因每个病例而异。 隔离的暴露 肾小球细胞增加浓度的所有这三个 促分泌素与膜去极化有关，但我们的 初步数据表明，这种情况发生的离子机制 在每种情况下都是不同的。 我们建议研究离子 分泌的电生理学相关物的机制和动力学 由这些药物治疗肾小球细胞引起。 实验 将对来自肾上腺的酶分离细胞进行 大鼠 这些研究将采用经典的电生理学方法， 以及最近发展起来的单电极电压钳技术 和膜片钳。 以下实验问题将得到解决：（1）我们将 检查肾小球细胞的基本电生理特性。 具体地，静息膜对Na+、K+、Cl-的渗透性将是 以及K+和Ca++电导的电压依赖性。 (2)我们将研究潜在的电生理事件 K+对激素分泌的调节。 (3)我们将调查 电生理事件伴随着分泌的调节， 促分泌素AII和ACTH以及那些潜在的机制， 其拮抗剂（即多巴胺、心房利钠因子等）在这些 细胞 在正常人和血压正常的大鼠中，钠限制和/或饮食 钾负荷增加肾小球细胞的反应性 它的秘密使者。 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， 看看这些敏感性变化的电生理学相关性是否可以 在这种情况下表现出来。 近50%的患者 高血压似乎缺乏这种钠介导反应性变化 敬所有人。 一种遗传性高血压大鼠（SHR）具有类似的 异常 我们将对血压正常（Sprague 道利）和自发性高血压（SHR）大鼠，旨在观察 饮食中钠或钾摄入量的变化改变了 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.