EFFECTS OF PHI ON NA+-H+, NA+-DEPENDENT, AND NA+- INDEPENDENT CL--HCO3- EXCHANGERS IN VASCULAR SMOOTH-MUSCLE

The mechanisms that control intracellular pH (pH(i)) in vascular smooth muscle are not fully understood. We reported that pH(i) in primary cultured vascular smooth muscle cells from canine femoral artery is 7.26, a value maintained via HCO3- influx by the Na+-dependent Cl(-)-HCO3- exchanger but not via H+ efflux by the Na+-H+ exchanger [A. M. Kahn, E.J. Cragoe, Jr., J. C. Allen, R. D. Halligan, and H. Shelat. Am. J. Physiol 259 (Cell Physiol. 28): C134-C143, 1990]. To explain these findings, in the present study, we determined the pH(i) activity profile of these two transport systems. Although both were active at acidic pH(i), Na+-H+ exchange activity was very low at and above pH(i) 7.0, while Na+-dependent Cl(-)-HCO3- exchange activity maintained near-maximal activity up to pH(i) 7.26 but fell to undetectable levels by pH(i) 7.4. A Na+-independent Cl(-)-HCO3- exchanger was present, which mediated HCO3- efflux after an acute alkaline load. The activity of this system was negligible at pH(i) 7.2 and was stimulated at alkaline pH(i). In conclusion, the pH(i) of these vascular smooth muscle cells at rest is maintained via HCO3- influx by the Na+-dependent Cl(-)-HCO3- exchanger. After acute acidic or alkaline loads, correction of pH(i) is mediated by activation of the normally quiescent Na+-H+ and Na+-independent Cl(-)-HCO3- exchangers, respectively. All three acid-base transport systems have pH(i) set points that protect the cell from overcorrecting pH(i) after a disturbance in either direction.