title: Coordinated regulation of intracellular K+ in the proximal tubule: Ba2+ blockade down-regulates the Na+,K+-ATPase and up-regulates two K+ permeability pathways.
abstract: To avoid large changes in cell K+ content and volume during variations in Na+,K+-ATPase activity, Na+-transporting epithelia must adjust the rate of K+ exit through passive permeability pathways. Recent studies have shown that a variety of passive K+ transport mechanisms may coexist within a cell and may be functionally linked to the activity of the Na+,K+-ATPase. In this study, we have identified three distinct pathways for passive K+ transport that act in concert with the Na+,K+-ATPase to maintain intracellular K+ homeostasis in the proximal tubule. Under control conditions, the total K+ leak of the tubules consisted of discrete Ba2+-sensitive (approximately 65%), quinine-sensitive (approximately 20%), and furosemide-sensitive (approximately 10%) pathways. Following inhibition of the principal K+ leak pathway with Ba2+, the tubules adaptively restored cell K+ content to normal levels. This recovery of cell K+ content was inhibited, in an additive manner, by quinine and furosemide. Following adaptation to Ba2+, the tubules exhibited a 30% reduction in Na+-K+ pump rate coupled with an increase in K+ leak by means of the quinine-sensitive (approximately 70%) and furosemide-sensitive (approximately 280%) pathways. Thus, the proximal tubule maintains intracellular K+ homeostasis by the coordinated modulation of multiple K+ transport pathways. Furthermore, these results suggest that, like Ba2+, other inhibitors of K+ conductance will cause compensatory changes in both the Na+-K+ pump and alternative pathways for passive K+ transport.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: B C
authors.initials: BC
authors.lastname: Kone
authors.forename: H R
authors.initials: HR
authors.lastname: Brady
authors.forename: S R
authors.initials: SR
authors.lastname: Gullans
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D010539:Permeability; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011803:Quinine / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D015221:Potassium Channels; D001464:Barium; D010042:Ouabain; D005665:Furosemide; D012964:Sodium; D011803:Quinine; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium