title: Millimolar amiloride concentrations block K conductance in proximal tubular cells.
abstract: 1. Amiloride, applied at millimolar concentrations, results in the blockade of K+ conductance in amphibian proximal convoluted cells (PCT), fused into giant cells. 2. Amiloride results directly in a blockade of K+ conductance that is not related to inhibition of the Na(+)-H+ antiport, which would lower intracellular pH, adversely affecting K+ conductance. On the contrary, high amiloride concentrations promote entry of this lipophilic base in the cell, leading to higher cell pH. 3. Under voltage clamp conditions, control vs. amiloride, current-voltage curves from PCT fused giant cells intersect at -86.2 +/- 3.4 mV, a value close to the equilibrium potential for potassium. 4. Hexamethylene amiloride, 10(-5) M, irreversibly depolarizes the membrane potential. 5. Barium decreased by 50% the initial slope of realkalinization, following removal of a solution containing NH4Cl, as did amiloride. In addition, these blockers reduced membrane conductance by 40%, suggesting that a fraction of the amiloride-suppressible NH4+ efflux may be conductive. 6. Amiloride does not directly inhibit the Na(+)-K+, ATPase in our preparation, contrary to the prevalent belief. 7. In vivo studies show that amiloride interferes with an apical K+ conductance but it does not alter basolateral K+ conductance.
authors.affiliation: INSERM U. 323, Faculté de Médecine Necker Enfants-Malades, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Discala
authors.forename: P
authors.initials: P
authors.lastname: Hulin
authors.forename: F
authors.initials: F
authors.lastname: Belachgar
authors.forename: G
authors.initials: G
authors.lastname: Planelles
authors.forename: A
authors.initials: A
authors.lastname: Edelman
authors.forename: T
authors.initials: T
authors.lastname: Anagnostopoulos
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002459:Cell Fusion; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009337:Necturus; D011188:Potassium / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D011895:Rana ridibunda; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D000644:Quaternary Ammonium Compounds; D001464:Barium; D000584:Amiloride; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium