Millimolar amiloride concentrations block K conductance in proximal tubular cells

Article date: October 1992

By: Françoise Discala, Philippe Hulin, Fouzia Belachgar, Gabrielle Planelles, Aleksander Edelman, Takis Anagnostopoulos, in Volume 107, Issue 2, pages 532-538

Amiloride, applied at millimolar concentrations, results in the blockade of K+ conductance in amphibian proximal convoluted cells (PCT), fused into giant cells.

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.

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.

Hexamethylene amiloride, 10−5m, irreversibly depolarizes the membrane potential.

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.

7In vivo studies show that amiloride interferes with an apical K+ conductance but it does not alter basolateral K+ conductance.

Amiloride, applied at millimolar concentrations, results in the blockade of K+ conductance in amphibian proximal convoluted cells (PCT), fused into giant cells.

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.

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.

Hexamethylene amiloride, 10−5m, irreversibly depolarizes the membrane potential.

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.

7In vivo studies show that amiloride interferes with an apical K+ conductance but it does not alter basolateral K+ conductance.

DOI: 10.1111/j.1476-5381.1992.tb12779.x

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