Role of BK channels in hypertension and potassium secretion.
Role of BK channels in hypertension and potassium secretion.
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DOI：
10.1097/mnh.0b013e3283488889
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发表时间：
2011-09
影响因子：
3.2
通讯作者：
Sansom SC
中科院分区：
文献类型：
--
作者：
Holtzclaw JD;Grimm PR;Sansom SC
目的总结近年来有关高血压与肾钾排泄缺陷相关的研究，并对钙激活钾通道（BK）在闰细胞中的钾分泌作用的新证据和理论进行综述。离体灌流小管方法揭示了BK在流量诱导的K分泌的重要性。随后，BK亚基基因缺失的小鼠揭示了BK介导的K分泌的复杂性。BKα缺失导致极度醛固酮增多症、高血压和缺乏血流诱导的K分泌。BKβ1辅助亚基的缺失导致钾负荷处理减少、血浆钾升高、轻度醛固酮增多症和高血压，高钾饮食可加重高血压。BKβ4（β4KO）的缺失导致钾处理不足、血浆钾升高、液体潴留，但伴有轻度高血压。β 4 KO中的液体潴留可能是流量诱导的ATP分泌不足的结果，ATP通常抑制上皮Na通道（ENaC）。敲除小鼠电解质处理的经典生理学分析启发了我们对肾脏K通道处理K负荷机制的理解。研究集中在BK-α/β1和BK-α/β4在肾脏中的不同作用。BKβ1高血压可能是一种“三击性”高血压，涉及钾分泌缺陷、醛固酮产生增加和血管张力增加。在BK基因敲除小鼠中观察到的疾病揭示了正确的肾脏K处理对维持容量平衡和血压的重要性的新见解。
To summarize recent studies of hypertension associated with a defect in renal K excretion due to genetic deletions of various components of the large, Ca-activated K channel (BK), and review new evidence and theories regarding K secretory roles of BK in intercalated cells. Isolated perfused tubule methods have revealed the importance of BK in flow-induced K secretion. Subsequently, mice with genetically deleted BK subunits revealed the complexities of BK-mediated K secretion. Deletion of the BKα results in extreme aldosteronism, hypertension and an absence of flow-induced K secretion. Deletion of the BKβ1 ancillary subunit results in decreased handling of a K load, increased plasma K, mild aldosteronism and hypertension that is exacerbated by a high K diet. Deletion of the BKβ4 (β4KO) leads to insufficient K handling, high plasma K, fluid retention, but with milder hypertension. Fluid retention in β4KO may be the result of insufficient flow-induced secretion of ATP, which normally inhibits epithelial Na channels (ENaC). Classical physiological analysis of electrolyte handling in knock-out mice has enlightened our understanding of the mechanism of handling K loads by renal K channels. Studies have focused on the different roles of the BK-α/β1 and BK-α/β4 in the kidney. BKβ1 hypertension may be a “three-hit” hypertension, involving a K secretory defect, elevated production of aldosterone, and increased vascular tone. The disorders observed in BK knock-out mice have shed new insights on the importance of proper renal K handling for maintaining volume balance and blood pressure.