Transport activities involved in intracellular pH recovery following acid and alkali challenges in rat brain microvascular endothelial cells |
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Authors: | Pieris A. Nicola Caroline J. Taylor Shanshan Wang Margery A. Barrand Stephen B. Hladky |
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Affiliation: | Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK. |
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Abstract: | 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, [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] across the blood-brain barrier. |
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Keywords: | Rat brain endothelial cells Bicarbonate transport pH regulation |
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