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Sarcolemmal mechanisms for pH_i recovery from alkalosis in the guinea-pig ventricular myocyte

Chae-Hun Leem and Richard D. Vaughan-Jones

1. The mechanism of pH_i recovery from an intracellular alkali load (induced by acetate prepulse or by reduction/removal of ambient P_CO2) was investigated using intracellular SNARF fluorescence in the guinea-pig ventricular myocyte.

2. In Hepes buffer (pH_o 7·40), pH_i 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).

3. In 5 % CO₂/HCO₃^- buffer (pH_o 7·40), pH_i 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.

4. At a test pH_i 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.

5. We conclude that two independent sarcolemmal acid-loading carriers are stimulated by a rise of pH_i 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.

6. 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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