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REGULATION OF BODY WATER AND ELECTROLYTES CONCENTRATIONS BY RENAL NA/K/2CL TRANSPORTER (NKCC2)

肾脏 NA/K/2CL 转运蛋白 (NKCC2) 对体内水份和电解质浓度的调节

基本信息

批准号：
11670050
负责人：
KAWAHARA Katsumasa
金额：
$ 1.6万
依托单位：
KITASATO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670050/
关键词：
potassium channel ROMK2 ROMK1 Kir7.1 cardiac infarction congenital heart failure potassium load rats K^+チャネル心筋梗塞ラット K^+負荷ラット腎髄質内層集合管 NKCC1 mRNA 高浸透圧ウエスタンブロット cycloheximide

项目摘要

It is known that abundance of the membrane transporter gene expression in kidney tubules changes during the period of either growing or aging. Its level is provably regulated by changes in the chemical or hormonal conditions of internal environment. Physiological and pathological changes in body fluid electrolytes, which are related with food intake, internal metabolism, and various diseases, may directly affect expression of the ion transporter mRNA.In order to investigate the factors which may regulate the gene expression, we have prepared two model animals : one is the potassium-loaded newborn rat and the other one is the rat with cardiac infarction. First, development of the renal potassium excretion capacity was studied in the newborn rats of 7-14 days which were acutely infused with the exogenous potassium. The onset of the extra potassium excretion was determined as 1.7 day. Time-course of the ROMK1 expression was in parallel increased with that of the extra potassium excretion. Time-courses of the ROMK2 and Kir7.1 expression were different. According to these results, a possible rate limiting step for potassium secretion is hypothesized as ROMK1 channel at the apical membrane of collecting ducts. Second, time-dependent changes in the expression of NHE1 mRNA and protein were investigated by using either RNase protection assay or Western blotting, respectively, in the rat with cardiac infarction. It seems to be strange that NHE1 protein decreased significantly at 5 h after the infarction, whereas NHE1 mRNA varied little in the same period. Decrease in sodium influx through a N+/H+ antiporter may protect the cardiac cell by decreasing ATP consumption of Na+/K+ ATPase. Regulation of the Na/K/2Cl transporter (NKCC2) mRNA expression by the secondary changes in electrolytes after cardiac infarction remains unsolved.

已知肾小管中膜转运蛋白基因表达的丰度在生长或衰老期间发生变化。可以证明，它的水平是由体内环境的化学或激素条件的变化所调节的。体液电解质的生理和病理变化与食物摄入、体内代谢和各种疾病有关，可直接影响离子转运体mRNA的表达。为了研究可能调控基因表达的因素，我们制备了两种模型动物：一种是钾负荷新生大鼠，另一种是心肌梗死大鼠。首先，研究了急性输注外源性钾后7 ~ 14天新生大鼠肾脏钾排泄能力的变化。额外的钾排泄开始于1.7天。ROMK1的表达随额外钾排泄量的增加而增加。ROMK2和Kir7.1表达的时间过程不同。根据这些结果，一个可能的钾分泌速率限制步骤被假设为收集管顶端膜上的ROMK1通道。其次，分别采用RNase保护法和Western blotting法研究心肌梗死大鼠NHE1 mRNA和蛋白表达的时间依赖性变化。奇怪的是，NHE1蛋白在梗死后5 h明显下降，而NHE1 mRNA在同一时期变化不大。钠通过N+/H+反转运蛋白流入的减少可能通过减少Na+/K+ ATP酶的ATP消耗来保护心肌细胞。心肌梗死后电解质的继发性变化对Na/K/2Cl转运体（NKCC2） mRNA表达的调控尚不清楚。