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REGULATION OF RENAL H+/K+ EXCHANGE

肾H/K交换的监管

基本信息

批准号：
2458790
负责人：
Randi Beth Silver
金额：
$ 13.11万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-08-01 至 2000-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2458790
关键词：
acid base balance aldosterone apical membrane basolateral membrane electrolyte balance hydrogen potassium exchanging ATPase hydrogen transport intracellular transport laboratory rabbit laboratory rat membrane transport proteins perfusion potassium renal tubular transport

项目摘要

The cortical collecting tubule (CCT) of the mammalian kidney is responsible for the final regulation of urine pH and potassium (K) concentration. The 2 major cell types involved in this regulation are the Na-transporting principal cells and the acid-base regulating intercalated cells. recent evidence suggests the presence of a gastric- type acid transporter (H-K ATPase) in the renal collecting duct. This proposal focuses on the contribution of a functionally identified H-K exchanger (H-K ATPase) to the process of acid-base and K homeostasis in intercalated cells of the cortical collecting tubule, utilizing fluorescence measurements of intracellular pH and calcium. Six specific aims will be addressed using three related preparations. The functional activity of the H-K exchanger will be monitored by measuring the rate of K-dependent intracellular pH recovery in response to an imposed acid load. the role of this exchanger in K reabsorption and H secretion and regulation by pH, K and aldosterone will be examined. Basic characterization of the H-K exchanger includes assessing the functional similarity of the exchanger to the well-characterized gastric H-K ATPase, apical/basolateral localization of the exchanger, and defining its contribution to intracellular pH regulation under basal conditions. Preparations appropriate to selected aims include: split open cortical collecting tubules, isolated parietal cells, and isolated perfused cortical collecting tubules, loaded with the intracellular pH indicator, BCECF or the intracellular Ca indicator, Fura-2. In addition, the unesterified forms of BCECF and PBFI, a K-specific indicator, will be used for perfused tubule studies. Functional characterization of an H-K exchange mechanism and localization of this mechanism may help explain a number of clinical observations: 1. the association between low serum K and extracellular alkalosis, 2. the relationship between metabolic acidosis and reduced excretion of K which can elevate serum K to a point where it interferes with electrical activity of the heart. The results of these studies will provide important information on normal and pathological K states and will influence our understanding of K balance during metabolic abnormalities and diuretic therapy.

哺乳动物肾脏的皮质集小管（CCT）为