MODULATION BY EXTRACELLULAR CL- OF VOLUME-ACTIVATED ORGANIC OSMOLYTE AND HALIDE PERMEABILITIES IN HELA-CELLS

Organic osmolyte and halide permeability pathways activated in epithel ial HeLa cells by osmotically induced cell swelling were studied using electrophysiological and radiotracer efflux techniques. On hypotonic challenge, HeLa cells responded by activating an efflux pathway for [H -3]taurine and a swelling-induced outwardly rectifying Cl(-)channel. R emoval of extracellular Cl-, or its replacement by a less permeable an ion, enhanced taurine efflux and decreased the inward current (Cl- eff lux). The effect of Cl- removal on taurine efflux was not a consequenc e of changes in membrane potential. The degree of deactivation of the Cl- current at depolarized potentials was also Cl- dependent, suggesti ng that external Cl- is necessary for channel activity. The Cl- channe l inhibitors 1,9-dideoxyforskolin, tamoxifen, and 4,4'-diisothiocyanos tilbene-2,2'-disulfonic acid (DIDS) inhibited swelling-activated tauri ne efflux, with DIDS being the most potent, at variance with the sensi tivity of the Cl- channel. DIDS effect was dependent on external Cl-; concentrations of DIDS that inhibited 50% of taurine efflux were 0.2 a nd 4 mu M at low and high Cl-, respectively. The results could be inte rpreted on the basis of separate pathways for swelling-activated tauri ne efflux and Cl- current differentially affected by Cl-. Alternativel y, taurine and Cl- flux might occur through a common channel, with the two solutes interacting within the pore and being affected differenti ally by Cl- replacement.