Relationships between short-circuit current (I-sc), cell Cl and the me
chanism(s) of Cl accumulation in toad bladder epithelial cells were in
vestigated. In serosal Cl-free gluconate Ringer, 80% of the cell Cl (m
easured by x-ray microanalysis) was lost over 30-60 min with an associ
ated decrease in cell water content. Concomitantly, I-sc fell to 20% o
f its initial value within 10 min but then recovered to 45% of its ini
tial value despite continued Cl loss. With the reintroduction of Cl, c
ell Cl and I-sc both recovered within 10 min. Serosal SITS etamido-4'-
isothiocyano-stilbene-2,2'-disulfonate; 0.5 mM) plus bumetanide (0.1 m
M), did not prevent the fall in I-sc or the loss of cell Cl in glucona
te medium, although they did inhibit subsequent recovery of I-sc in th
is medium. They also prevented the recovery of I-sc in Cl medium but n
ot the reaccumulation of Cl by the cells. Although SITS and bumetanide
did not prevent the loss or recovery of Cl, they modified the pattern
of the ion changes. In their absence, changes in cellular Cl were twic
e that of the changes in measured cellular cations implicating basolat
eral Cl/HCO3 exchange in Cl movement. With SITS plus bumetanide presen
t, changes of similar magnitude in Cl were associated with equivalent
changes in cation, consistent with the inhibition of Cl/HCO3 exchange.