Amiloride reduces potassium conductance in frog kidney via inhibition of Na+-H+ exchange

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Abstract
The existence of a carrier-mediated Na+-H+ exchange has been described recently in many epithelial and nonepithelial tissues including the diluting segment of the amphibian kidney. In this preparation the Na+-H+ exchanger is dramatically stimulated by so-called K+ adaptation (chronic exposure of animals to high potassium) and completely inhibited by the diuretic drug amiloride. We performed electrophysiological experiments in diluting segments of the isolated perfused frog kidney to investigate whether amiloride affects the conductance properties of this epithelium. Amiloride dramatically increased the transepithelial resistance and the ratio of lumen over peritubular cell membrane resistance. Cell membrane potential changes, induced by luminal K+ concentration steps, were blunted by luminal application of amiloride, by luminal Na+-free perfusates, or by acidification of the kidney perfusion solution. K+ secretory net flux, measured by K+-sensitive microelectrodes, decreased by half in presence of the diuretic. The experiments reveal that amiloride reduces the K+ conductance of the luminal cell membrane of frog diluting segment via inhibition of the luminal Na+-H+ exchanger. This decreases transepithelial K+ net secretion in this nephron segment.