Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet.

Abstract

Type II Bartter's syndrome is a hereditary hypokalemic renal salt-wasting disorder caused by mutations in the ROMK channel (Kir1.1; Kcnj1), mediating potassium recycling in the thick ascending limb of Henle's loop (TAL) and potassium secretion in the distal tubule and cortical collecting duct (CCT). Newborns with Type II Bartter are transiently hyperkalemic, consistent with loss of ROMK channel function in potassium secretion in distal convoluted tubule and CCT. Yet, these infants rapidly develop persistent hypokalemia owing to increased renal potassium excretion mediated by unknown mechanisms. Here, we used free-flow micropuncture and stationary microperfusion of the late distal tubule to explore the mechanism of renal potassium wasting in the Romk-deficient, Type II Bartter's mouse. We show that potassium absorption in the loop of Henle is reduced in Romk-deficient mice and can account for a significant fraction of renal potassium loss. In addition, we show that iberiotoxin (IBTX)-sensitive, flow-stimulated maxi-K channels account for sustained potassium secretion in the late distal tubule, despite loss of ROMK function. IBTX-sensitive potassium secretion is also increased in high-potassium-adapted wild-type mice. Thus, renal potassium wasting in Type II Bartter is due to both reduced reabsorption in the TAL and K secretion by max-K channels in the late distal tubule.

• Authors: M A Bailey, A Cantone, Q Yan, G G MacGregor, Q Leng, J B O Amorim, T Wang, S C Hebert, G Giebisch, G Malnic
• Journal: Kidney international (Kidney Int) Vol. 70 Issue 1 Pg. 51-9 (Jul 2006) ISSN: 0085-2538 [Print] United States
• PMID: 16710355 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Kcnj1 protein, mouse
• Large-Conductance Calcium-Activated Potassium Channels
• Peptides
• Potassium Channels, Inwardly Rectifying
• Potassium, Dietary
• iberiotoxin
• Potassium

Topics

• Adaptation, Physiological
• Animals
• Bartter Syndrome (genetics, metabolism)
• Biological Transport
• Diet
• Disease Models, Animal
• Hypokalemia (genetics, metabolism)
• Kidney Tubules, Distal (drug effects, metabolism)
• Large-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors, physiology)
• Loop of Henle (drug effects, physiology)
• Mice
• Mice, Mutant Strains
• Peptides (pharmacology)
• Potassium (metabolism, urine)
• Potassium Channels, Inwardly Rectifying (deficiency, genetics)
• Potassium, Dietary (administration & dosage)