Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
Curr Opin Nephrol Hypertens. 2011 Sep;20(5):512-7. doi: 10.1097/MNH.0b013e3283488889.
This review summarizes 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 describes 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 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 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 adenosine triphosphate (ATP), which normally inhibits epithelial Na channels (ENaCs).
Classical physiological analysis of electrolyte handling in knockout mice has enlightened our understanding of the mechanism of handling K loads by renal K channels. Studies have focused on the different roles of 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 knockout mice have shed new insights on the importance of proper renal K handling for maintaining volume balance and blood pressure.
本文综述了由于大电导钙激活钾通道（BK）的各种成分的基因缺失导致肾排钾缺陷相关高血压的近期研究，并描述了 BK 在闰细胞钾分泌中的作用的新证据和理论。
分离灌注的管状方法揭示了 BK 在流量诱导的钾分泌中的重要性。随后，BK 基因缺失的小鼠揭示了 BK 介导的钾分泌的复杂性。BKα 缺失导致极端的醛固酮症、高血压和流量诱导的钾分泌缺失。BKβ1 辅助亚基的缺失导致对钾负荷的处理能力降低，血浆钾增加，轻度醛固酮症和高血压，高钾饮食会使高血压恶化。BKβ4 缺失（β4KO）导致钾处理不足，血浆钾高，液体潴留，但高血压较轻。β4KO 中的液体潴留可能是由于流量诱导的三磷酸腺苷（ATP）分泌不足，ATP 通常会抑制上皮钠通道（ENaC）。
对敲除小鼠电解质处理的经典生理学分析使我们对肾脏钾通道处理钾负荷的机制有了更深入的了解。研究集中在 BK-α/β1 和 BK-α/β4 在肾脏中的不同作用。BKβ1 型高血压可能是一种“三击”高血压，涉及钾分泌缺陷、醛固酮产量增加和血管张力增加。在 BK 敲除小鼠中观察到的疾病为适当的肾脏钾处理对于维持容量平衡和血压的重要性提供了新的见解。
