Distal potassium handling based on flow modulation of maxi-K channel activity.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Rodan
Aylin R
AR
Division of Nephrology, Department of Medicine, UT Southwestern Medical Center, Dallas, Texas 75390-8856, USA. aylin.rodan@utsouthwestern.edu
Huang
Chou-Long
CL
D000818:Animals; D001477:Bartter Syndrome / Q000209:etiology; D006801:Humans; D007679:Kidney Medulla / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011546:Pseudohypoaldosteronism / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D049992:Sodium Chloride Symporters / Q000502:physiology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D049992:Sodium Chloride Symporters; D012964:Sodium; D017346:Protein Serine-Threonine Kinases; C433806:WNK4 protein, human; D011188:Potassium