VOLUME-SENSITIVE ANION CHANNELS MEDIATE SWELLING-ACTIVATED INOSITOL AND TAURINE EFFLUX

C6 glioma cells accumulate the organic osmolyte inositol in response t o chronic hypertonic stress. Upon return to isotonic conditions, cell swelling activates a Na+-independent passive low-affinity inositol eff lux mechanism that is inhibited 80-100% by a number of anion transport blockers, certain lipoxygenase blockers, and various polyunsaturated fatty acids. Taurine efflux is also enhanced by cell swelling. The tau rine efflux pathway has characteristics that are identical to those of the inositol efflux mechanism, including kinetics of activation and i nactivation, osmotic sensitivity, pharmacological sensitivity, and inh ibition by certain Na+ and Cl- substitutes. These results suggest stro ngly that volume-sensitive inositol and taurine efflux are mediated by a common transport mechanism. The inhibition of the transport pathway by anion transport blockers and unsaturated fatty acids suggests indi rectly that efflux of these solutes may be mediated by an anion channe l. Whole cell patch clamp measurements in CsCl solutions were used to test this hypothesis. Under hypertonic conditions, C6 cells had an ext remely low membrane conductance (approximately 0.02 nS/pF). After cell swelling, however, whole cell anion conductance was activated rapidly to values up to 1.5-2 nS/pF. This conductance was outwardly rectified and selective for anions and was inhibited 80-100% by blockers of swe lling-activated inositol and taurine efflux. The relative taurine perm eability (i.e., P(taurine)/P(Cl)) of the conductance was 0.20. Isosmot ic replacement of raffinose in the external medium with inositol or so rbitol induced a transient inward current, suggesting that Cl- and the se polyols compete for common binding sites on the channel. We conclud e that a volume-sensitive anion channel mediates the efflux of structu rally diverse organic osmolytes such as taurine and inositol from the cell.