Cytotoxic effect of choline, abolished by furosemide, in the diluting segment of frog kidney

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Abstract
Previous observations suggest that luminal application of tetra-N-alkylammonium ions may impair ion transport in the amphibian diluting segment. To investigate this question conventional KCl-filled and Cl− sensitive microelectrodes were applied in diluting segments of the isolated perfused kidney ofrana esculenta to evaluate transepithelial electrical and chloride electrochemical (PDte, E te Cl ) as well as peritubular cell membrane potential difference (PDpt), measured at static head conditions. After determination of control values the tubule lumen was exposed to choline (95 mmol/l, substituted for Na+) both in presence or absence of furosemide (5×10−5 mol/l). Then, the lumen was again perfused with control solution and the measurements were repeated. Thus, a time course for possible choline induced effects was obtained both in the presence and absence of furosemide. The lumen positive PDte decreased from 11.2±1.0 mV to 6.3±0.8 mV after 2 min and to 1.9±0.4 mV after 30 min exposure to choline. PDpt (cell interior negative) decreased from 70±2 mV to 58±3 mV and to 42±5 mV after 2 and 30 min, respectively. Intraluminal Cl− activity increased from its initial steady state value of 20±2 mol/l to 39±2 mmol/l after 30 min exposure to choline. However, if the tubule lumen was exposed to choline. in presence of furosemide (5×10−5 mol/l), all the above described choline-induced effects did not become apparent. The data are consistent with the hypothesis that choline traverses the cell membrane via the furosemide-sensitive cotransport system, accumulates in the cell cytosol, blocks luminal K+ conductance and by this means inhibits transepithelial ion transport. Thus, longterm exposure of furosemide-sensitive epithelia to choline and its derivatives should be avoided.