Rodan Aylin R, Huang Chou-Long
Division of Nephrology, Department of Medicine, UT Southwestern Medical Center, Dallas, Texas 75390-8856, USA.
Curr Opin Nephrol Hypertens. 2009 Jul;18(4):350-5. doi: 10.1097/MNH.0b013e32832c75d8.
Studies on the mechanisms of distal K+ secretion have highlighted the importance of the renal outer-medullary K+ (ROMK) and maxi-K channels. This review considers several human disorders characterized by hypokalemia and hyperkalemia, as well as mouse models of these disorders, and the mechanisms by which ROMK and maxi-K may be dysregulated.
Analysis of knockout mice lacking ROMK, a model for type II Bartter's syndrome, has shown a role for maxi-K in distal K+ secretion. Knockout mice lacking either the alpha or beta1 subunits of maxi-K also show deficits in flow-dependent K+ secretion. Analysis of transgenic and knock-in mouse models of pseudohypoaldosteronism type II, in which mutant forms of with-no-lysine kinase 4 are expressed, suggests ways in which ROMK and maxi-K may be dysregulated to result in hyperkalemia. Modeling studies also provide insights into the role of Na+ delivery vs. flow in K+ secretion.
The importance of both ROMK and maxi-K to distal K+ secretion is now well established, but the relative role that each of these two channels plays in normal and diseased states has not been definitively established. Analysis of human and animal model data can generate hypotheses for future experiments.
关于远端钾离子分泌机制的研究突出了肾外髓质钾离子（ROMK）通道和大电导钙激活钾通道（maxi-K）的重要性。本综述探讨了几种以低钾血症和高钾血症为特征的人类疾病及其小鼠模型，以及ROMK和maxi-K通道可能失调的机制。
对缺乏ROMK的基因敲除小鼠（II型巴特综合征模型）的分析表明，maxi-K在远端钾离子分泌中起作用。缺乏maxi-K的α或β1亚基的基因敲除小鼠也表现出流量依赖性钾离子分泌缺陷。对II型假性醛固酮增多症的转基因和基因敲入小鼠模型（其中表达了无赖氨酸激酶4的突变形式）的分析，提示了ROMK和maxi-K可能失调导致高钾血症的方式。模型研究也为钠离子输送与流量在钾离子分泌中的作用提供了见解。
现在已经充分证实了ROMK和maxi-K对远端钾离子分泌的重要性，但这两种通道在正常和疾病状态下各自所起的相对作用尚未明确确定。对人类和动物模型数据的分析可为未来实验提出假设。
