Transport activities involved in intracellular pH recovery following acid and alkali challenges in rat brain microvascular endothelial cells.
Transport activities involved in intracellular pH (pH(i)) recovery after acid or alkali challenge were investigated in cultured rat brain microvascular endothelial cells by monitoring pH(i) using a pH-sensitive dye. Following relatively small acid loads with pH(i) approximately 6.5, HCO(-)(3) influx accounted for most of the acid extrusion from the cell with both Cl(-)-independent and Cl(-)-dependent, Na(+)-dependent transporters involved. The Cl(-)-independent component has the same properties as the NBC-like transporter previously shown to account for most of the acid extrusion near the resting pH(i). Following large acid loads with pH(i) < 6.5, most of the acid extrusion was mediated by Na(+)/H(+) exchange, the rate of which was steeply dependent on pH(i). Concanamycin A, an inhibitor of V-type ATPase, had no effect on the rates of acid extrusion. Following an alkali challenge, the major component of the acid loading leading to recovery of pH(i) occurred by Cl(-)/HCO(-)(3) exchange. This exchange had the same properties as the AE-like transporter previously identified as a major acid loader near resting pH(i). These acid-loading and acid-extruding transport mechanisms together with the Na(+), K(+), ATPase may be sufficient to account not only for pH(i) regulation in brain endothelial cells but also for the net secretion of HCO(-)(3) across the blood-brain barrier.
Nicola
Pieris A
PA
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
Taylor
Caroline J
CJ
Wang
Shanshan
S
Barrand
Margery A
MA
Hladky
Stephen B
SB
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000378:metabolism; D000143:Acids / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000468:Alkalies / Q000378:metabolism*; D000584:Amiloride / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D002254:Carbonates / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008833:Microcirculation; D018696:Neuroprotective Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
D000143:Acids; D000468:Alkalies; D002254:Carbonates; D002712:Chlorides; D018696:Neuroprotective Agents; D000584:Amiloride; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D012964:Sodium; D025262:Vacuolar Proton-Translocating ATPases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C039614:ethylisopropylamiloride