SWELLING-ACTIVATED ANION CONDUCTANCE IN SKATE HEPATOCYTES - REGULATION BY CELL C1(-) AND ATP

Cell swelling activates an outwardly rectifying anion conductance in m ammalian cells. The channel responsible for this conductance mediates volume-regulatory efflux of organic osmolytes such as taurine. We obse rved a similar conductance in hepatocytes from the skate Raja erinacea . Whole cell Cl- conductance was increased > 100-fold by a 2-fold incr ease in hepatocyte volume. The conductance was outwardly rectifying an d had a relative cation permeability of similar to 0.2. Cation permeab ility was increased by reductions in patch pipette CsCl concentration, suggesting that the channel pore contains saturable anion and cation binding sites with different anion and cation affinities. The conducta nce had a broad anion selectivity and a relative taurine permeability of 0.17. Activation of the conductance required intracellular ATP or a nonhydrolyzable ATP analogue. Elevation of intracellular Cl- from 20 to 155 mM reduced current activation while the rate and extent of cell swelling were unaffected. Reduction of intracellular Cl- concentratio n to 5-10 mM caused spontaneous current activation without cell swelli ng. These results suggest that increases in cell Cl- levels increase t he volume set point of the channel. We propose that the main function of the outwardly rectifying anion channel is nonselective transport of organic solutes.