Sarcolemmal mechanisms for pHi recovery from alkalosis in the guinea‐pig ventricular myocyte

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Abstract
The mechanism of pHi recovery from an intracellular alkali load (induced by acetate prepulse or by reduction/removal of ambient PCO2) was investigated using intracellular SNARF fluorescence in the guinea‐pig ventricular myocyte. In Hepes buffer (pHo 7.40), pHi recovery was inhibited by removal of extracellular Cl−, but not by removal of Na+o or elevation of K+o. Recovery was unaffected by the stilbene drug DIDS (4,4‐diisothiocyanatostilbene‐disulphonic acid), but was slowed dose dependently by the stilbene drug DBDS (dibenzamidostilbene‐disulphonic acid). In 5 % CO2/HCO3− buffer (pHo 7.40), pHi recovery was faster than in Hepes buffer. It consisted of an initial rapid recovery phase followed by a slow phase. Much of the rapid phase has been attributed to CO2‐dependent buffering. The slow phase was inhibited completely by Cl− removal but not by Na+o removal or K+o elevation. At a test pHi of 7.30 in CO2/HCO3− buffer, the slow phase was inhibited 70 % by DIDS. The mean DIDS‐inhibitable acid influx was equivalent in magnitude to the HCO3−‐stimulated acid influx. Similarly, the DIDS‐insensitive influx was equivalent to that estimated in Hepes buffer. We conclude that two independent sarcolemmal acid‐loading carriers are stimulated by a rise of pHi and account for the slow phase of recovery from an alkali load. The results are consistent with activation of a DIDS‐sensitive Cl−‐HCO3− anion exchanger (AE) to produce HCO3− efflux, and a DIDS‐insensitive Cl−‐OH− exchanger (CHE) to produce OH− efflux. H+‐Cl− co‐influx as the alternative configuration for CHE is not, however, excluded. The dual acid‐loading system (AE plus CHE), previously shown to be activated by a fall of extracellular pH, is thus activated by a rise of intracellular pH. Activity of the dual‐loading system is therefore controlled by pH on both sides of the cardiac sarcolemma.

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