Aldosterone activates Na⁺/H⁺ exchange and raises cytoplasmic pH in target cells of the amphibian kidney

The hypothesis was tested if the mineralocorticoid hormone aldosterone stimulates Na⁺/H⁺ exchange in 'giant cells' fused from individual target cells of the distal nephron of the frog kidney. By means of microelectrodes, steady-state intracellular pH (pH(i)) and pH(i) recovery from an acid load were recorded continuously while the fused cells were exposed to aldosterone. Twenty minutes after addition of the hormone, pH(i) started to rise and reached a new steady state after about 60 min (ΔpH(i) = 0.28 ± 0.01). After hormone treatment, pH(i) recovered significantly faster in response to an intracellular acid load. The diuretic drug amiloride blocked pH(i) recovery. Experiments in intact tubules showed that aldosterone induces H⁺ and K⁺ secretion. Thus, intracellular alkalosis, mediated by Na⁺/H⁺ exchange, could serve as a signal that activates pH-sensitive K⁺ channels of the luminal cell membrane.