MATURATION OF CATION TRANSPORT IN DISTAL NEPHRON

远端肾单位中阳离子传输的成熟

• 批准号: 6380562
• 负责人: Lisa M. Satlin
• 金额: $ 34.33万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380562
• 关键词: apical membrane; calcium indicator; corticosteroids; gene expression; genetic library; genetic transcription; growth /development; hormone regulation /control mechanism; infant animal; laboratory rabbit; laboratory rat; northern blottings; polymerase chain reaction; potassium channel; protein isoforms; protein kinase; protein structure function; renal tubular transport; saluresis; sodium channel; sodium potassium exchanging ATPase; voltage /patch clamp

DESCRIPTION (Adapted from the Applicant's Abstract): The final regulation of urinary K+ and Na+ excretion is accomplished in the renal cortical collecting duct (CCC). In this segment, urinary Na+ diffuses into principal cells through apical Na+ channels (ENaCs) and is extruded at the basolateral membrane in exchange for uptake of K+ by the Na-K pump. Cell K+ then passively diffuses out of the cell down a favorable electrochemical gradient into the luminal fluid through apical K+-selective (SK) channels. Kidneys of full term neonates efficiently retain urinary K+ and Na+, as is necessary for growth. In contrast to the high rates of net K+ secretion observed in CCDs isolated from adult animals and microperfused in vitro, segments from neonatal animals show no significant K+ transport and a paucity of apical SK channels. Yet, the same neonatal segments possess conducting ENaC channels and absorb Na+ at a rate half that measured in the adult. The focus of this application is to examine the cellular and molecular mechanisms mediating the postnatal activation of apical 5K and ENaC channels, those rate-limiting pathways for K+ and Na+ transport in the CCD. The hypotheses we propose to examine, as they relate to the SK (Specific Aim 1) and Na+ (Specific Aim 2) channel, are focussed first on discerning whether the appearance of conducting channels is regulated by transcription, translation, and/or post-translational processing. Thereafter, we will identify those circulating (adrenal corticosteroids) and cytoplasmic (kinases, Ca2+) factors prevailing early in life that regulate gene and protein expression. ion channel activity, and tubular transport in the developing CCD. These studies will be accomplished using a combination of molecular, electrophysiologic, and functional techniques. The long-term goal of this study is to identify the cellular and molecular mechanisms responsible for the regulation and interaction of Na+ and K+ transport in the principal cell. These studies should help us understand the physiologic basis for inherited and acquired disorders associated with electrolyte imbalance, disorders which carry a high morbidity.

描述（根据申请人的摘要改编）：最终法规 在肾皮质中完成了尿K+和Na+排泄 收集管道（CCC）。 在此部分中，尿液Na+扩散成主 细胞通过顶端Na+通道（ENAC），并在基底外侧挤出 膜以换取Na-K泵对K+的吸收。 然后 被动地从细胞中散开一个有利的电化学梯度 通过顶端K+选择性（SK）通道进入腔流体。 肾脏 必要的 为了增长。 与在 从成年动物和体外微养殖的CCD，来自 新生动物没有明显的K+转运和顶端SK的稀少 频道。 然而，相同的新生儿段具有导电的ENAC通道 并以成年人测量的一半吸收Na+。 重点 应用是检查介导的细胞和分子机制 顶端5K和ENAC通道的产后激活，这些限制 CCD中K+和Na+传输的途径。 我们建议的假设 检查与SK（特定目标1）和Na+相关时（特定目标2） 渠道，首先将重点放在识别出现是否出现 通过转录，翻译和/或 翻译后处理。 此后，我们将确定 循环（肾上腺皮质类固醇）和细胞质（激酶，Ca2+） 在调节基因和蛋白质表达的早期生命早期普遍存在的因素。 发育中的CCD中的离子通道活性和管状转运。 这些 研究将使用分子的组合来完成 电生理和功能技术。 这个长期目标 研究是为了确定负责的细胞和分子机制 主体中Na+和K+传输的调节和相互作用 细胞。 这些研究应帮助我们了解生理基础 与电解质不平衡相关的遗传和获得的疾病， 发病率高的疾病。