CELLULAR MECHANISMS--TUBULOGLOMERULAR FEEDBACK SYSTEM

细胞机制--管球反馈系统

• 批准号: 6041807
• 负责人: Phillip Darwin Bell
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6041807
• 关键词: adenosine; angiotensin II; arterioles; calcium flux; cell cell interaction; cellular polarity; fluorescence microscopy; intracellular transport; ion transport; laboratory rabbit; membrane potentials; nitric oxide; potassium channel; renal glomerulus; renal tubular transport; renal tubule; thromboxanes; transforming growth factors; voltage /patch clamp

Macula densa cells serve in the transmission of information from tubular fluid to vascular elements through the tubuloglomerular feedback mechanism (TGF). Changes in luminal fluid [NaCl] are sufficient to activate the feedback pathway resulting in information flow from macula densa cells through the mesangial cell field and to the afferent arteriole. At the afferent arteriole, TGF signals result in alterations in membrane potential and changes in cytosolic calcium concentration ([Ca2+]i) through voltage dependent calcium channels. Our previous studies have focused on defining transport systems that operate at the macula densa since understanding these transport pathways should provide substantial insights into the TGF signaling process. With the use of microelectrodes, patch clamp techniques and fluorescence microscopy we have established the existence of apical Na:2Cl:K cotransport, Na:H exchange, K+ channel activity and a predominate CI- conductive pathway at the basolateral membrane. The purpose of these studies is to further our understanding of macula densa transport pathways and how these pathways may contribute to the generation of TGF signals using isolated perfused thick ascending limbs with attached glomeruli from rabbit kidney. The specific aims of this project are to: I) further characterize and examine the regulation of the major transport pathways located at the apical and basolateral membranes of macula densa cells; 2) determine the effects of intracellular messenger systems and physiological regulators of TGF including angiotensin Il, nitric oxide, thromboxane and adenosine on overall macula densa NaCI transport and membrane potential and 3) correlate changes in macula densa membrane potential, NaCI transport and intracellular messenger systems with TGF mediated alterations in afferent arteriole membrane potential and [Ca2+]i. These studies should provide important new insights into the generation and transmission of tubuloglomerular feedback signals from macula densa cells to arteriolar contractile elements.

致密黄斑细胞负责传递信息 管状液体通过肾小球到达血管元件 反馈机制（TGF）。管腔液体 [NaCl] 的变化是 足以激活产生信息的反馈途径 从致密斑细胞流经系膜细胞区并到达 传入小动脉。在传入小动脉，TGF 信号导致 膜电位的变化和胞质钙的变化 通过电压依赖性钙通道的浓度（[Ca2+]i）。 我们之前的研究重点是定义交通系统 自从了解这些运输以来，在致密斑进行操作 途径应该提供对 TGF 信号传导的深入了解 过程。使用微电极、膜片钳技术 和荧光显微镜我们已经确定了存在 顶端 Na:2Cl:K 共转运、Na:H 交换、K+ 通道活性 以及基底外侧的主要 CI 传导通路 膜。这些研究的目的是进一步我们 了解致密斑运输途径以及这些途径如何 使用以下途径可能有助于 TGF 信号的产生 分离的灌注厚升肢，附有肾小球 兔肾。该项目的具体目标是： I) 进一步 描述并检查主要交通运输的监管 位于黄斑顶膜和基底外侧膜的通路 致密细胞； 2) 确定细胞内信使的作用 TGF 的系统和生理调节剂，包括血管紧张素 II、一氧化氮、血栓素和腺苷对整个致密斑的影响 NaCl 转运和膜电位以及 3) 的相关变化 致密斑膜电位、氯化钠转运和细胞内 具有 TGF 介导的传入改变的信使系统 小动脉膜电位和 [Ca2+]i。这些研究应该 为发电和传输提供重要的新见解 致密斑细胞的管状肾小球反馈信号 小动脉收缩成分。