Millimolar amiloride concentrations block K conductance in proximal tubular cells

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 NH 4 Cl, as did amiloride. In addition, these blockers reduced membrane conductance by 40%, suggesting that a fraction of the amiloride‐suppressible NH 4 + 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.