Biophysical Journal 73: 674-687 (1997)
© 1997 the Biophysical Society

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rybak, S L Articles by Murphy, R F Search for Related Content PubMed PubMed Citation Articles by Rybak, S L Articles by Murphy, R F

Theoretical considerations on the role of membrane potential in the regulation of endosomal pH.

Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

ABSTRACT

Na+,K(+)-ATPase has been observed to partially inhibit acidification of early endosomes by increasing membrane potential, whereas chloride channels have been observed to enhance acidification in endosomes and lysosomes. However, little theoretical analysis of the ways in which different pumps and channels may interact has been carried out. We therefore developed quantitative models of endosomal pH regulation based on thermodynamic considerations. We conclude that 1) both size and shape of endosomes will influence steady-state endosomal pH whenever membrane potential due to the pH gradient limits proton pumping, 2) steady-state pH values similar to those observed in early endosomes of living cells can occur in endosomes containing just H(+)-ATPases and Na+,K(+)-ATPases when low endosomal buffering capacities are present, and 3) inclusion of active chloride channels results in predicted pH values well below those observed in vivo. The results support the separation of endocytic compartments into two classes, those (such as early endosomes) whose acidification is limited by attainment of a certain membrane potential, and those (such as lysosomes) whose acidification is limited by the attainment of a certain pH. The theoretical framework and conclusions described are potentially applicable to other membrane-enclosed compartments that are acidified, such as elements of the Golgi apparatus.

This article has been cited by other articles:

				M. Erent, A. Meli, N. Moisoi, V. Babich, M. J. Hannah, P. Skehel, L. Knipe, G. Zupancic, D. Ogden, and T. Carter Rate, extent and concentration dependence of histamine-evoked Weibel Palade body exocytosis determined from individual fusion events in human endothelial cells J. Physiol., August 15, 2007; 583(1): 195 - 212. [Abstract] [Full Text] [PDF]

				J. A. Covi and S. C. Hand V-ATPase expression during development of Artemia franciscana embryos: potential role for proton gradients in anoxia signaling J. Exp. Biol., July 15, 2005; 208(14): 2783 - 2798. [Abstract] [Full Text] [PDF]

				N.D. Sonawane and A.S. Verkman Determinants of [Cl-] in recycling and late endosomes and Golgi complex measured using fluorescent ligands J. Cell Biol., March 31, 2003; 160(7): 1129 - 1138. [Abstract] [Full Text] [PDF]

				M. Gekle, O. K. Serrano, K. Drumm, S. Mildenberger, R. Freudinger, B. Gassner, H. W. Jansen, and E. I. Christensen NHE3 serves as a molecular tool for cAMP-mediated regulation of receptor-mediated endocytosis Am J Physiol Renal Physiol, September 1, 2002; 283(3): F549 - F558. [Abstract] [Full Text] [PDF]

				Q.-R. Chen, L. Zhang, P. W. Luther, and A. J. Mixson Optimal transfection with the HK polymer depends on its degree of branching and the pH of endocytic vesicles Nucleic Acids Res., March 15, 2002; 30(6): 1338 - 1345. [Abstract] [Full Text] [PDF]

				N. D. Sonawane, J. R. Thiagarajah, and A. S. Verkman Chloride Concentration in Endosomes Measured Using a Ratioable Fluorescent Cl- Indicator. EVIDENCE FOR CHLORIDE ACCUMULATION DURING ACIDIFICATION J. Biol. Chem., February 8, 2002; 277(7): 5506 - 5513. [Abstract] [Full Text] [PDF]

				Y. Li, T. Kane, C. Tipper, P. Spatrick, and D. D. Jenness Yeast Mutants Affecting Possible Quality Control of Plasma Membrane Proteins Mol. Cell. Biol., May 1, 1999; 19(5): 3588 - 3599. [Abstract] [Full Text] [PDF]

				J. Farinas and A. S. Verkman Receptor-mediated Targeting of Fluorescent Probes in Living Cells J. Biol. Chem., March 19, 1999; 274(12): 7603 - 7606. [Abstract] [Full Text] [PDF]

				N. A. BRADBURY Intracellular CFTR: Localization and Function Physiol Rev, January 1, 1999; 79(1): 175 - 191. [Abstract] [Full Text] [PDF]

				N. Bayer, D. Schober, E. Prchla, R. F. Murphy, D. Blaas, and R. Fuchs Effect of Bafilomycin A1 and Nocodazole on Endocytic Transport in HeLa Cells: Implications for Viral Uncoating and Infection J. Virol., December 1, 1998; 72(12): 9645 - 9655. [Abstract] [Full Text] [PDF]

				K. Teter, G. Chandy, B. Quinones, K. Pereyra, T. Machen, and H.-P. H. Moore Cellubrevin-targeted Fluorescence Uncovers Heterogeneity in the Recycling Endosomes J. Biol. Chem., July 31, 1998; 273(31): 19625 - 19633. [Abstract] [Full Text] [PDF]

				F. B. Schapiro and S. Grinstein Determinants of the pH of the Golgi Complex J. Biol. Chem., July 7, 2000; 275(28): 21025 - 21032. [Abstract] [Full Text] [PDF]

				M. Numata and J. Orlowski Molecular Cloning and Characterization of a Novel (Na+,K+)/H+ Exchanger Localized to the trans-Golgi Network J. Biol. Chem., May 11, 2001; 276(20): 17387 - 17394. [Abstract] [Full Text] [PDF]