1. The role of chloride and bicarbonate in the control of intracellular pH (pH(i)) was assessed in segments of rat mesenteric resistance arteries (internal diameter about 200-mu-m) by measurements of chloride efflux with Cl-36-, of pH(i) with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5 (and-6)-carboxyfluorescein (BCECF) and of membrane potential with intracellular electrodes. 2. The main questions addressed were whether the previously demonstrated sodium-coupled uptake of bicarbonate in these arteries was also coupled to chloride efflux, and whether sodium-independent Cl(-)-HCO3- exchange was present and played a role in regulation of pH(i). 3. The Cl-36- efflux was unaffected by acidification induced by an NH4Cl pre-pulse in the presence as well as in the absence of bicarbonate. This was also true in sodium-free media and in vessels depolarized by high potassium. 4. The membrane potential was unaffected by the acidification associated with wash-out of NH4Cl, and the net acid extrusion during recovery of pH(i) from the acidification was not affected significantly by depolarization. 5. In the absence of bicarbonate, omission of extracellular chloride caused no change in pH(i), but reduced Cl-36- efflux. By contrast, in the presence of bicarbonate, omission of chloride caused an increase in pH(i), but no change in Cl-36- efflux. Furthermore, the anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) inhibited the increase in pH(i) seen in the presence of bicarbonate and reduced the Cl-36- efflux in the presence of bicarbonate. 6. The presence of bicarbonate had no significant effect on the rate of recovery of pH(i) or the rate of increase of intracellular acid equivalents after an NH4Cl induced alkalinization; also the buffering power was not significantly different in the absence and presence of bicarbonate. Moreover these parameters were not significantly affected by DIDS, although DIDS as previously demonstrated reduced the rate of recovery of pH(i) from acidification. 7. The membrane potential was not significantly affected by the alkalinization associated with addition of NH4Cl and the rate of recovery of pH(i) from the alkalinization was not affected by depolarization. 8. The effects of NH4Cl and P(CO2) on Cl-36- efflux were complex and could not easily be explained by the changes in pH(i). 9. We conclude that in these resistance arteries an electroneutral Na+-HCO3- co-transport plays an important role for the recovery of pH(i) from an acid load, and that a sodium-independent Cl(-)-HCO3- exchange exists which can operate in a Cl(-)-Cl- exchange mode although this system may be of only minor importance for control of pH(i). Furthermore, it was not possible to demonstrate a sodium-dependent Cl(-)-HCO3- exchange.
