INTRACELLULAR IONIC-STRENGTH REGULATES THE VOLUME SENSITIVITY OF A SWELLING-ACTIVATED ANION CHANNEL

Cell swelling activates an outwardly rectifying anion channel termed V SOAC (volume-sensitive organic osmolyte/anion channel). Regulation of VSOAC by intracellular electrolytes was characterized in Chinese hamst er ovary cells by whole cell patch clamp. Elevation of intracellular C sCl concentration from 40 to 180 mM resulted in a concentration-depend ent decrease in channel activation. Activation of VSOAC was insensitiv e to the salt gradient across the plasma membrane, the intracellular c oncentration of specific anions or cations, and the total intracellula r concentration of cations, anions, or electrolytes. Comparison of cel ls dialyzed with either CsCl or Na2SO4 solutions demonstrated directly that VSOAC activation is modulated by intracellular ionic strength (m u(i)) The relative cell volume at which VSOAC current activation was t riggered, termed the channel volume set point, decreased with decreasi ng ionic strength. At mu(i) = 0.04, VSOAC activation occurred spontane ously in shrunken cells. The rate of VSOAC activation mras nearly 50-f old higher in cells with mu(i) = 0.04 vs. those with mu(i) = 0.18. We propose that mu(i) modulates the volume sensor responsible for channel activation.