The role of ion antiporters in the maintenance of intracellular pH in rat vascular smooth muscle cells.

Vascular smooth muscle intracellular pH is maintained by the Na+/H+ and Cl-/HCO3- antiporters. The Na+/H+ exchanger is a major route of H+ extrusion in most eukaryotic cells and is present in vascular smooth muscle cells in a similar capacity. It extrudes H+ into the extracellular space in exchange for Na+. The Cl-/HCO3- exchanger plays an analogous role to lower the pH of vascular smooth muscle cells when increases in intracellular pH occur. Its activity has also been demonstrated in A7r5 and A10 vascular smooth muscle cells. The Na+/H+ exchanger is regulated by a number of agents which act through inositol trisphosphate/diacylglycerol, to stimulate the antiporter. Calcium-calmodulin dependent protein kinase may also activate the antiporter in vivo. Phosphorylation of the Cl-/HCO3- exchanger has also been observed but its physiological role is not known. Both these antiporters exist in the plasma membrane as integral proteins with free acidic cytoplasmic termini. These regions may be important in 'sensing' changes in intracellular pH, to which these antiporters respond.