THEORETICAL CONSIDERATIONS ON THE ROLE OF MEMBRANE-POTENTIAL IN THE REGULATION OF ENDOSOMAL PH

Na+,K+-ATPase has been observed to partially inhibit acidification of early endosomes by increasing membrane potential, whereas chloride cha nnels have been observed to enhance acidification in endosomes and lys osomes. However, little theoretical analysis of the ways in which diff erent pumps and channels may interact has been carried out. We therefo re developed quantitative models of endosomal pH regulation based on t hermodynamic considerations. We conclude that 1) both size and shape o f endosomes will influence steady-state endosomal pH whenever membrane potential due to the pH gradient limits proton pumping, 2) steady-sta te pH values similar to those observed in early endosomes of living ce lls can occur in endosomes containing just H+-ATPases and Na+,K+-ATPas es when low endosomal buffering capacities are present, and 3) inclusi on of active chloride channels results in predicted pH values well bel ow those observed in vivo. The results support the separation of endoc ytic compartments into two classes, those (such as early endosomes) wh ose acidification is limited by attainment of a certain membrane poten tial, and those (such as lysosomes) whose acidification is limited by the attainment of a certain pH. The theoretical framework and conclusi ons described are potentially applicable to other membrane-enclosed co mpartments that are acidified, such as elements of the Golgi apparatus .