An electrophysiological study of angiotensin II regulation of Na-HCO3 cotransport and K conductance in renal proximal tubules. I. Effect of picomolar concentrations.
The effect of picomolar concentrations of angiotensin II (AII) was investigated in isolated perfused rabbit renal proximal tubules using conventional or pH-sensitive intracellular microelectrodes. Under control conditions cell membrane potential (Vb) and cell pH (pHi) averaged -53.8 +/- 1.9 mV (mean +/- SEM, n = 49) and 7.24 +/- 0.01 (n = 10), respectively. AII (at 10(-11) mol/l), when applied from the bath (but not when applied from the lumen perfusate), produced the following effects: approximately 85% of the viable tubules responded with a small depolarization (+5.5 +/- 0.4 mV, n = 43) which was accompanied in half of the pHi measurements by a slow acidification (delta pHi = -0.03 +/- 0.01, n = 5). The remaining 15% responded with a small hyperpolarization (delta Vb = -3.1 +/- 0.4 mV, n = 6). All changes were fully reversible and repeatable. Experiments with fast changes in bath HCO3 or K concentrations, as well as measurements of the basolateral voltage divider fraction in response to transepithelial current flow, explain these observations as stimulation of a basolateral Na-HCO3 cotransporter and of a basolateral K conductance. Both counteract in their effect on Vb, but can be individuated by blocker experiments with 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and barium. Both the stimulation of Na-HCO3 cotransport and the stimulation of the K conductance may result from down-regulation of the level of cyclic adenosine monophosphate in the cell.
Coppola
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Zentrum der Physiologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.
Frömter
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism*; D008839:Microelectrodes; D009994:Osmolar Concentration; D011188:Potassium / Q000502:physiology*; D011817:Rabbits; D027982:Sodium-Bicarbonate Symporters
D002352:Carrier Proteins; D027982:Sodium-Bicarbonate Symporters; D000804:Angiotensin II; D001464:Barium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium