Role of chloride transport in regulation of intracellular pH

Abstract

IT is well known that introducing acid into a cell causes a rapid fall in intracellular pH (pH_i) which is followed by a slower rise^1–5. Since this return of pH_i towards its original value could not be accounted for by the passive transmembrane movement of H⁺, OH⁻, or HCO₃⁻, it was ascribed to the active removal of acid from the cell^1,2. In the squid giant axon, this acid extrusion is reversibly blocked by cyanide and greatly enhanced by HCO₃⁻/CO₂ (ref. 3). More recently, it has been found that acid extrusion in the snail neurone also is stimulated by HCO₃⁻/CO₂ (ref. 4), and that, in addition, it is inhibited by 4-acetamido-4′-isothiocyano-stilbene-2,2′-disulphonic acid (SITS)⁵, a known inhibitor of anion fluxes in erythrocytes⁶. In this respect it is interesting to note that a component of Cl⁻ efflux in barnacle muscle also is stimulated by HCO₃⁻/CO₂ and blocked by SITS⁷. We now report that acid extrusion in the squid axon requires internal Cl⁻ and ATP, that it is blocked by SITS, and that it is accompanied by the SITS-sensitive efflux of an equivalent amount of Cl⁻. These observations suggest that acid extrusion actually involves the neutral exchange of external HCO₃⁻ for internal Cl⁻.