Effects of extracellular bicarbonate ions and pH on volume-regulatory taurine efflux from rat cerebral cortical slices in vitro: evidence for separate neutral and anionic transport mechanisms.
Net efflux of [3H]taurine from cells in pre-loaded slices of rat cerebral cortex has previously been shown to occur via an anionic pathway, believed to consist of exchange of anionic taurine for extracellular Cl-, and operating under both isomotic and hypoosmotic conditions, and a calmodulin-dependent mechanism, activated by hypoosmotic stress: the latter may comprise conductive channels (Law, R.O. (1994) Biochim. Biophys. Acta 1221, 21-28). Experiments have now been performed to examine two inter-related problems; firstly, how anion/anion exchange (assuming 1:1 stochiometry) could contribute to the regulation of brain cell volume, and secondly, whether the hypoosmotically-activated component of efflux represents a second anionic transport process or loss of neutral taurine. The former process has been shown to be strongly dependent upon extracellular pH and bicarbonate concentration, being accelerated by low pH (7.0) and high (60 mmol/l) bicarbonate, and retarded by alkalinization (pH 7.8) and low (2.5 mmol/l) bicarbonate. Taurine efflux is inhibited by acetazolamide, with accompanying cell swelling in both isoosmotic and hypoosmotic media. It is hypothesized that inwardly directed bicarbonate transport, in exchange for intracellular Cl-, operates in parallel with efflux of anionic taurine in exchange for extracellular Cl-, and it is the subsequent conversion of bicarbonate to CO2 and water, under the influence of carbonic anhydrase, that effects a volume-regulatory decrease in internal osmotic potential. The dependence of taurine efflux upon pH and bicarbonate persists in the presence of trifluoperazine (an inhibitor of calmodulin activation) but is abolished in hypoosmotic media by the anion transport inhibitor niflumic acid. Cell depolarization in high K+ has no effect on taurine efflux, which is envisaged as involving parallel electroneutral anion exchange processes (taurine/Cl- and Cl-/bicarbonate) augmented, in hypoosmotic media, by diffusive efflux of neutral taurine.
Law
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Department of Cell Physiology and Pharmacology, University of Leicester, UK.
D000818:Animals; D000838:Anions; D001639:Bicarbonates / Q000494:pharmacology*; D001692:Biological Transport; D002540:Cerebral Cortex / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009994:Osmolar Concentration; D051381:Rats; D013654:Taurine / Q000378:metabolism*
D000838:Anions; D001639:Bicarbonates; D002712:Chlorides; D013654:Taurine