ROLE OF SENSING OF K+ INTAKE IN K+ HOMEOSTASIS

钾摄入量传感在钾稳态中的作用

• 批准号: 6841687
• 负责人: JANG H. YOUN
• 金额: $ 16.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-15 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6841687
• 关键词: biological signal transduction; denervation; dietary potassium; excretion; extracellular; homeostasis; ion transport; kidney function; laboratory rat; portal vein; potassium ion

DESCRIPTION (provided by applicant): Extracellular (ECF) K+ homeostasis is critical for normal cardiovascular and neuromuscular functions and is maintained by renal and extrarenal mechanisms. We recently developed the K clamp technique, which can quantify both renal K+ excretion and extrarenal cellular K+ uptake in vivo. Using this technique, we demonstrated that both renal K+ excretion and extrarenal cellular K+ uptake are rapidly and profoundly suppressed during K+ deprivation. These changes for ECF K+ conservation have been traditionally explained to arise from decreased ECF K+ levels and/or consequent decrease in aldosterone secretion. However, we found that this triggering of ECF K+ conservation can occur in rats in the absence of changes in plasma [K +] or [aldosterone] when K+ intake is reduced to 1/3 of control. The objective of this project is to test the hypothesis that K+ intake is sensed by K+ sensors in the portal vein, and both renal K+ excretion and extrarenal cellular K+ uptake are regulated by this signal. To achieve this goal, we will collaborate with Dr. Casey Donovan at our institution and employ strategies similar to those used to demonstrate the presence of portal vein glucose sensors in rats, i.e., "local irrigation" and portal denervation techniques. Our preliminary data showed that reducing K+ intake to 1/3 of normal for only one night (12 h) was sufficient to trigger marked renal K+ conservation. In the proposed studies we will use this overnight low K+ feeding model to address the following specific aims. Aim 1. Test for the existence of portal (or splanchnic) sensing of Kv intake and its regulation of renal and extrarenal K+ handling. We will test whether the triggering of ECF K+ conservation by overnight low dietary K+ intake is prevented by parallel K+ supplementation via intragastric or intraportal infusion, which would be sensed by the hypothetical portal vein (or splanchnic) sensors, but not by K+ supplementation via systemic infusion. Aim 2. Test for a role of portal sensing of K+ intake in extracellular K+ homeostasis. We propose to test whether portal denervation ablates portal sensing of Kv intake and, if so, whether it impairs the acute and chronic regulation of ECF K+ homeostasis by delaying renal and extrarenal responses to altered K+ intake. Significance: This project will potentially identify an important, previously unknown regulator of ECF K+ homeostasis.

描述（由申请人提供）：细胞外（ECF）K+稳态对于正常的心血管和神经肌肉功能至关重要，并且通过肾脏和外肾外机制维持。我们最近开发了K夹技术，该技术可以量化体内肾脏K+排泄和肾外细胞+摄取。使用此技术，我们证明了肾脏K+排泄和肾外细胞+摄取均在K+剥夺期间迅速而深刻地抑制。传统上，ECF K+保护的这些变化是由ECF K+水平降低和醛固酮分泌下降引起的。但是，我们发现，在缺乏血浆[K+]或[醛固酮]的情况下，当K+进气降低到对照的1/3时，这种触发ECF K+保护可能会发生在大鼠中。该项目的目的是检验以下假设：门静脉中的K+传感器感测K+的摄入量，并且肾脏K+排泄和肾外细胞K+摄取均受该信号的调节。为了实现这一目标，我们将与我们机构的凯西·多诺万（Casey Donovan）博士合作，并采用类似于证明大鼠中门静脉葡萄糖传感器的策略，即“局部灌溉”和门户的神经膜技术。我们的初步数据表明，将K+摄入量减少到正常的1/3仅一晚（12小时）就足以触发标记的肾脏K+保护。在拟议的研究中，我们将使用此隔夜低K+进食模型来解决以下特定目标。 AIM 1。测试KV摄入量的门户（或斑点）感应及其对肾脏和外K+处理的调节。我们将测试是否通过胃内或胃中输液中的K+补充平行的K+摄入来触发ECF K+保存是否可以防止其触发，而K+摄入量是通过胃内或内部输液的补充，这将通过假设的门静脉静脉（或SplanchNIC）传感器来感知，但不能通过通过系统输注来获得K+补充K+。 AIM 2。测试在细胞外K+稳态中K+摄入量的门户传感的作用。我们建议测试门户网神经是否消除了KV摄入量的门户传感，以及是否会通过延迟对K+摄入量改变的肾脏和外反应来损害ECF K+稳态的急性和慢性调节。 意义：该项目可能会确定一个重要的，以前未知的ECF K+稳态调节剂。