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+ 稳态对于正常心血管和神经肌肉功能至关重要，并由肾脏和肾外机制维持。我们最近开发了 K 钳技术，该技术可以量化体内肾 K+ 排泄和肾外细胞 K+ 摄取。使用这种技术，我们证明了在 K+ 剥夺期间，肾脏 K+ 排泄和肾外细胞 K+ 摄取均受到快速而深刻的抑制。 ECF K+ 保守性的这些变化传统上被解释为 ECF K+ 水平降低和/或随之而来的醛固酮分泌减少所致。然而，我们发现，当 K+ 摄入量减少至对照组​​的 1/3 时，在血浆 [K +] 或 [醛固酮] 没有变化的情况下，大鼠中可能会触发 ECF K+ 保守。该项目的目的是检验以下假设：门静脉中的 K+ 传感器感知 K+ 摄入量，并且肾脏 K+ 排泄和肾外细胞 K+ 摄取均受该信号调节。为了实现这一目标，我们将与我们机构的 Casey Donovan 博士合作，并采用类似于用于证明大鼠门静脉葡萄糖传感器存在的策略，即“局部冲洗”和门静脉去神经技术。我们的初步数据表明，仅一晚（12 小时）将 K+ 摄入量减少至正常值的 1/3 就足以引发显着的肾脏 K+ 保存。在拟议的研究中，我们将使用这种隔夜低 K+ 喂养模型来实现以下具体目标。 目标 1. 测试 Kv 摄入的门静脉（或内脏）感应是否存在及其对肾脏和肾外 K+ 处理的调节。我们将测试通过胃内或门静脉内输注平行补充 K+ 是否可以防止隔夜低膳食 K+ 摄入量触发 ECF K+ 守恒，假设的门静脉（或内脏）传感器可以感知到这一点，但通过全身补充 K+ 却不能感知到这一点。输液。 目标 2. 测试 K+ 摄入的门静脉感应在细胞外 K+ 稳态中的作用。我们建议测试门静脉去神经术是否消除了 Kv 摄入的门静脉感应，如果是的话，它是否会通过延迟肾脏和肾外对 K+ 摄入量变化的反应来损害 ECF K+ 稳态的急性和慢性调节。 意义：该项目将有可能发现一个重要的、以前未知的 ECF K+ 稳态调节因子。