Grimm P Richard, Sansom Steven C
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
Curr Opin Nephrol Hypertens. 2007 Sep;16(5):430-6. doi: 10.1097/MNH.0b013e32826fbc7d.
Large, BK (calcium-activated potassium) channels are now regarded as relevant players in many aspects of renal physiology, including potassium secretion. This review will highlight recent discoveries regarding the function and localization of BK in the kidney.
Patch clamp electrophysiology has revealed BK in cultured podocytes, glomerular mesangial cells, and in several tubule segments including principal cells (connecting tubules/principal cells), and intercalated cells of connecting tubules and cortical collecting ducts. Flow-induced potassium secretion is mediated by BK in the distal nephron and may be partly the result of shear stress-induced increases in cell calcium concentrations. ROMK-/- and wild-type mice on a high potassium diet exhibit BK-mediated potassium secretion, and studies of BK-alpha-/- and BK-beta1-/- mice suggest that flow-induced potassium secretion is mediated by BK-alpha/beta1, which is specifically localized in the apical membrane of the connecting tubule of the mouse and connecting tubule plus initial cortical collecting duct of the rabbit.
BK channels, located in glomerular cells and in many nephron segments, especially mediate potassium secretion in the combined condition of potassium adaptation and high flow. Understanding the molecular makeup of BK in specific renal cells and the dietary and physiological conditions for their expression can yield improved potassium-sparing compounds.
大电导钙激活钾(BK)通道目前被认为是肾脏生理学多个方面的相关参与者,包括钾分泌。本综述将重点介绍关于BK在肾脏中的功能和定位的最新发现。
膜片钳电生理学研究揭示,BK存在于培养的足细胞、肾小球系膜细胞以及包括主细胞(连接小管/主细胞)、连接小管和皮质集合管的闰细胞在内的多个肾小管节段中。远端肾单位中,BK介导了流体诱导的钾分泌,这可能部分是剪切应力诱导细胞钙浓度升高的结果。高钾饮食条件下的ROMK-/-和野生型小鼠表现出BK介导的钾分泌,对BK-α-/-和BK-β1-/-小鼠的研究表明,流体诱导的钾分泌由BK-α/β1介导,该通道特异性定位于小鼠连接小管的顶膜以及兔子连接小管和初始皮质集合管中。
BK通道存在于肾小球细胞和许多肾单位节段中,尤其在钾适应和高流量的联合条件下介导钾分泌。了解特定肾细胞中BK的分子组成及其表达的饮食和生理条件,可能会产生更好的保钾化合物。