Chloride secretion in kidney distal epithelial cells (A6) evoked by cadmium.
The effect of Cd(2+) on chloride secretion was examined in A6 renal epithelia cells by chloride-sensitive fluorescence (SPQ probe) and by the short-circuit-current (I(sc)) technique. Depleting the cells of Cl(-) suggests that the Cd(2+)-activated I(sc) (DeltaI(sc(Cd))) is dependent on the presence of Cl(-) ions. Among the Cl(-)-channel inhibitors the fenemates, flufenamic acid (FFA) and niflumic acid (NFA), and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) significantly lowered DeltaI(sc(Cd)) compared with control level. In SPQ-loaded A6 cells, Cd(2+) evoked an increase in Cl(-) secretion ([DeltaCl(-)](Cd)), which significantly exceeded the basal Cl(-) transport and was blockable by FFA and NFA. The closely related metals, Zn(2+) or Ni(2+), were also able to activate Cl(-) secretion. Preexposure of Zn(2+) or Ni(2+) completely prevented [DeltaCl(-)](Cd), suggesting that Zn(2+) and Ni(2+) probably use similar mechanisms. Like Cd(2+), thapsigargin (TG), an inhibitor of intracellular Ca(2+)-ATPase and the Ca(2+)-ionophore A23187, induced an increase in I(sc). Moreover, TG and Cd(2+) were able to neutralize the responses of the counterparts as also observed in I(sc) measurements, which indicates that Cd(2+) activates Cl(-) secretion in a Ca(2+)-dependent manner. Hence, this study supports the idea that basolateral Cd(2+) (possibly also Zn(2+) and Ni(2+)), probably through a Ca(2+)-sensing receptor, causes calcium mobilization that activates apical fenemate-sensitive chloride channels leading to chloride secretion in A6 cells.
Faurskov
B
B
Grenaa Central Hospital, Sygehusuej 6, 8500, Grenaa, Denmark. bf@get2net.dk
Bjerregaard
H F
HF
D000465:Algorithms; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004594:Electrophysiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008670:Metals / Q000633:toxicity; D018408:Patch-Clamp Techniques; D013050:Spectrometry, Fluorescence; D014982:Xenopus laevis
D018118:Chloride Channels; D002712:Chlorides; D005456:Fluorescent Dyes; D008670:Metals; D002104:Cadmium; D002118:Calcium