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Am J Physiol Heart Circ Physiol 291: H1147-H1157, 2006. First published May 5, 2006; doi:10.1152/ajpheart.00166.2006
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Vacuolar-type H+-ATPases at the plasma membrane regulate pH and cell migration in microvascular endothelial cells

J. D. Rojas,1,* S. R. Sennoune,1,* D. Maiti,1 K. Bakunts,1 M. Reuveni,5 S. C. Sanka,1 G. M. Martinez,1 E. A. Seftor,6 C. J. Meininger,3 G. Wu,4 D. E. Wesson,1,2 M. J. C. Hendrix,6 and R. Martínez-Zaguilán1

Departments of 1Physiology and 2Internal Medicine, Texas Tech University Health Sciences Center, Lubbock; 3Department of Medical Physiology, Texas A & M University System Health Science Center, Temple; and 4Department of Animal Science, Texas A & M University, College Station, Texas; 5Department of Ornamental Horticulture, ARO Volcani Center, Bet-Dagan, Israel; and 6Children's Memorial Research Center, Northwestern University Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois

Submitted 14 February 2006 ; accepted in final form 24 March 2006

Microvascular endothelial cells involved in angiogenesis are exposed to an acidic environment that is not conducive for growth and survival. These cells must exhibit a dynamic intracellular (cytosolic) pH (pHcyt) regulatory mechanism to cope with acidosis, in addition to the ubiquitous Na+/H+ exchanger and HCO3–-based H+-transporting systems. We hypothesize that the presence of plasmalemmal vacuolar-type proton ATPases (pmV-ATPases) allows microvascular endothelial cells to better cope with this acidic environment and that pmV-ATPases are required for cell migration. This study indicates that microvascular endothelial cells, which are more migratory than macrovascular endothelial cells, express pmV-ATPases. Spectral imaging microscopy indicates a more alkaline pHcyt at the leading than at the lagging edge of microvascular endothelial cells. Treatment of microvascular endothelial cells with V-ATPase inhibitors decreases the proton fluxes via pmV-ATPases and cell migration. These data suggest that pmV-ATPases are essential for pHcyt regulation and cell migration in microvascular endothelial cells.

fluorescence spectroscopy; carboxyseminaphthorhodafluor-1; bafilomycin; sodium/hydrogen exchanger; buffering capacity; proton fluxes; migration; macrovascular endothelial cells


Address for reprint requests and other correspondence: R. Martínez-Zaguilán, Dept. of Physiology, Texas Tech Univ. Health Sciences Center, 3601 4th St., Lubbock, TX 79430-6551 (e-mail: Raul.MartinezZaguilan{at}ttuhsc.edu)




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