Control of Renal Na and K Excretion
控制肾脏钠和钾的排泄
基本信息
- 批准号:9284457
- 负责人:
- 金额:$ 58.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-06-01 至 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdrenergic AgonistsAgonistAldosteroneAngiotensin IIAngiotensinsAutonomic nervous systemBiotinylationChronicCorticosteroneDefectDietDiseaseDistalDistal convoluted renal tubule structureDiureticsDuct (organ) structureElectrophysiology (science)Endocrine systemEquilibriumExcretory functionFamilial diseaseGoalsHealthHomeostasisHormonesHypertensionIn SituInfusion proceduresIntakeIonsKCNJ1 geneKidneyMeasurementMeasuresMediatingMembrane ProteinsMethodsMineralocorticoid ReceptorMusMutateNatureNephronsNeurotransmittersPathologicPhosphotransferasesPhysiologicalPlasmaProteinsRattusRegulationReninResearchRoleSLC12A3 geneSaltsSignal TransductionSurfaceTechniquesTestingTransgenesTransport ProcessUp-Regulationdietary manipulationepithelial Na+ channelin vivoinsightmutantosmotic minipumppatch clamppublic health relevanceresponsesalt balance
项目摘要
DESCRIPTION (provided by applicant): We will investigate the mechanisms underlying control of renal Na and K excretion and their interactions. To this end, we will bring several complementary approaches to the problem, including in vivo microperfusion of distal convoluted tubules, electrophysiological analysis of connecting tubules and collecting ducts, and quantification of surface membrane proteins in the intact kidney. We will employ these techniques under conditions of changes in dietary Na and K intake, alterations in hormone status and several disease states and their treatments. The proposed research will test several related hypotheses on the nature of this regulation. First, alterations in transporters in the distl convoluted tubule (NaCl cotransport or NCC) and in the aldosterone-sensitive distal nephron, comprising the connecting tubule and collecting ducts (Na (ENaC) and K ROMK) channels) are the most important transport mechanisms involved in this regulation. Second, changes in Na balance will produce parallel changes in NCC and ENaC, while changes in K balance produce parallel changes in ENaC and ROMK, but antiparallel changes in NCC and ENaC. Third, the renin-angiotensin- aldosterone axis is a key hormonal system involved in this regulation, with ENaC controlled mainly by aldosterone, and NCC by angiotensin II. Fourth, the autonomic nervous system contributes to the overall regulation by selectively stimulating NCC. We will also use these approaches to investigate to the disorder of Familial Hyperkalemic Hypertension (FHHt). Specifically, we will examine the roles of WNK kinases - which are mutated in some forms of FHHt - in the regulation of Na and K excretion. The results will provide insight into how two segments of the nephron, together with two circulating hormones, cooperate in order to maintain Na and K balance in the face of a range of dietary challenges and pathological insults.
描述(由申请人提供):我们将研究肾脏钠和钾排泄的控制机制及其相互作用。为此,我们将采用几种补充方法来解决该问题,包括远曲小管的体内微灌注、连接小管和集合管的电生理学分析以及完整肾脏中表面膜蛋白的定量。我们将在膳食钠和钾摄入量变化、激素状态变化以及几种疾病状态及其治疗的情况下采用这些技术。拟议的研究将测试有关该法规性质的几个相关假设。首先,远曲小管(NaCl 共转运或 NCC)和醛固酮敏感远端肾单位(包括连接小管和集合管(Na (ENaC) 和 K ROMK) 通道)中转运蛋白的改变是最重要的转运机制在此规定中。其次,Na平衡的变化会产生NCC和ENaC的平行变化,而K平衡的变化会产生ENaC和ROMK的平行变化,但NCC和ENaC的反平行变化。第三,肾素-血管紧张素-醛固酮轴是参与该调节的关键激素系统,ENaC主要受醛固酮控制,NCC主要受血管紧张素II控制。第四,自主神经系统通过选择性刺激NCC来促进整体调节。我们还将使用这些方法来研究家族性高钾性高血压 (FHHt) 疾病。具体来说,我们将研究 WNK 激酶(在某些形式的 FHHt 中发生突变)在调节 Na 和 K 排泄中的作用。研究结果将深入了解肾单位的两个部分与两种循环激素如何合作,以在面临一系列饮食挑战和病理损伤时维持钠和钾的平衡。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Down-regulation of PRKCB1 expression in Han Chinese patients with subsyndromal symptomatic depression.
中国汉族亚综合征症状性抑郁症患者 PRKCB1 表达下调。
- DOI:10.1016/j.jpsychires.2015.07.011
- 发表时间:2015-10-01
- 期刊:
- 影响因子:4.8
- 作者:Xiaoyun Guo;Zezhi Li;Chen Zhang;Z. Yi;Haozhe Li;L. Cao;C. Yuan;W. Hong;Zhi;D. Peng;Jun Chen;Weiping Xia;Guoqing Zhao;Fan Wang;Shun;D. Cui;Yifeng Xu;Chowdhury M I Golam;Alicia K. Smith;Tong Wang;Yi
- 通讯作者:Yi
Role of potassium channels in female reproductive system.
钾通道在女性生殖系统中的作用。
- DOI:
- 发表时间:2020-09
- 期刊:
- 影响因子:0
- 作者:Kim, Jun;Song, Ki;Xu, Boqun;Wang, Tong
- 通讯作者:Wang, Tong
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LAWRENCE G PALMER其他文献
LAWRENCE G PALMER的其他文献
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{{ truncateString('LAWRENCE G PALMER', 18)}}的其他基金
Regulation of ENaC Trafficking and Activity in the Kidney
ENaC 贩运和肾脏活动的监管
- 批准号:
10558733 - 财政年份:2017
- 资助金额:
$ 58.05万 - 项目类别:
Regulation of ENaC Trafficking and Activity in the Kidney
ENaC 贩运和肾脏活动的监管
- 批准号:
10363434 - 财政年份:2017
- 资助金额:
$ 58.05万 - 项目类别:
Epithelial Na Channels and Regulation of Na Excretion
上皮钠通道和钠排泄的调节
- 批准号:
7903717 - 财政年份:2009
- 资助金额:
$ 58.05万 - 项目类别:
Epithelial Na Channels and Regulation of Na Excretion
上皮钠通道和钠排泄的调节
- 批准号:
6470312 - 财政年份:2002
- 资助金额:
$ 58.05万 - 项目类别:
Epithelial Na Channels and Regulation of Na Excretion
上皮钠通道和钠排泄的调节
- 批准号:
8220927 - 财政年份:2002
- 资助金额:
$ 58.05万 - 项目类别:
Epithelial Na Channels and Regulation of Na Excretion
上皮钠通道和钠排泄的调节
- 批准号:
6727498 - 财政年份:2002
- 资助金额:
$ 58.05万 - 项目类别:
Epithelial Na Channels and Regulation of Na Excretion
上皮钠通道和钠排泄的调节
- 批准号:
7460111 - 财政年份:2002
- 资助金额:
$ 58.05万 - 项目类别:
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