Role of chloride transport in regulation of intracellular pH

• DOI: 10.1038/264073a0
• Publication Date: 2005-08-03T16:15:38Z
• Authors: JOHN M. RUSSELL; WALTER F. BORON
• Keywords: Intracellular pH; Efflux

IT is well known that introducing acid into a cell causes a rapid fall in intracellular pH (pHi) which is followed by a slower rise1–5. Since this return of pHi 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 cell1,2. 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−.