Cytoplasmic pH determines K+ conductance in fused renal epithelial cells.
The mineralocorticoid hormone aldosterone maintains acid-base balance and K+ homeostasis by regulating H+ and K+ secretory mechanisms in kidney epithelial cells. We have shown recently in the amphibian distal nephron that aldosterone activates a Na+/H+ exchange system in the luminal cell membrane, thus leading to transepithelial H+ secretion and cytoplasmic alkalinization. Since H+ secretory fluxes were paralleled by K+ secretion, it was postulated that the hormone-induced increase of intracellular pH activates the luminally located K+ channels. In "giant" cells fused from individual cells of the distal nephron, we measured simultaneously cytoplasmic pH and cell membrane K+ conductance during acidification of the cell cytoplasm. The experiments show that cell membrane K+ conductance is half-maximal at an intracellular pH of 7.42 and that a positive cooperative interaction exists between K+-channel proteins and H+ (Hill coefficient = 6.5). Moreover, the cellular K+ conductance is most sensitive to cytoplasmic pH in the range modified by aldosterone. This supports the hypothesis that intracellular H+ activity, regulated by the Na+/H+ exchanger, serves as the signal to couple aldosterone-induced K+ secretory flux to H+ secretion in renal tubules.
Oberleithner
H
H
Department of Physiology, University of Würzburg, Federal Republic of Germany.
Kersting
U
U
Hunter
M
M
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D004848:Epithelium / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism*; D007668:Kidney / Q000166:cytology*; D008839:Microelectrodes; D011188:Potassium / Q000378:metabolism*; D011894:Rana pipiens; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D007473:Ion Channels; D017923:Sodium-Hydrogen Exchangers; D001464:Barium; D011188:Potassium