Effects of inhibitors of Cl conductance on Cl self-exchange in rabbit cortical collecting tubule.
Electroneutral vs. conductive pathways of Cl transport were examined by measuring transepithelial conductance (GT) and the lumen-to-bath 36Cl rate coefficient (KCl). Experimental conditions minimized both Cl-HCO3 exchange [HCO3/CO2-free, N-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid (HEPES)-buffered solutions] and the electrical driving force for paracellular Cl diffusion (amiloride in the perfusate, transepithelial voltage near zero). Two agents known to inhibit Cl conductances in other epithelia, anthracene-9-carboxylate (9AC, 1 mM) and diphenylamine carboxylate (DPC, 0.1-0.5 mM) reversibly reduced GT and KCl when added to the bath. Both reduced KCl to values consistent with paracellular diffusion. Bath DPC had no effect on GT in the presence of 4 mM lumen Ba2+, suggesting that the DPC-sensitive conductance is in series with an apical K conductance, i.e., resides on the basolateral membrane. Lumen DPC also reduced GT and KCl, but was less potent than bath DPC. Because the lumen DPC effect on GT was also blocked by lumen Ba2+, lumen DPC probably inhibits a basolateral Cl conductance. K removal and ouabain (0.5 mM) had no effect on KCl, suggesting that Cl tracer movement is not predominantly through the principal cell. We assume that these agents are inhibiting Cl conductive pathways and propose a model in which transcellular Cl movement through the intercalated cell occurs via an apical electroneutral entry step in series with a basolateral conductive pathway.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D004553:Electric Conductivity; D004848:Epithelium / Q000502:physiology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits
D002121:Calcium Channel Blockers; D002712:Chlorides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D010042:Ouabain; D000584:Amiloride