Vacuolar-type H+-ATPases at the plasma membrane regulate pH and cell migration in microvascular endothelial cells

Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1147-57. doi: 10.1152/ajpheart.00166.2006. Epub 2006 May 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / enzymology*
  • Cell Membrane / physiology
  • Cell Movement / physiology*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology*
  • Hydrogen-Ion Concentration
  • Immunohistochemistry
  • Microcirculation / physiology
  • Rats
  • Rats, Inbred BB
  • Sodium-Hydrogen Exchangers / physiology
  • Vacuolar Proton-Translocating ATPases / metabolism*


  • Sodium-Hydrogen Exchangers
  • Vacuolar Proton-Translocating ATPases