Intracellular ionic strength regulates the volume sensitivity of a swelling-activated anion channel

Cell swellingactivates an outwardly rectifying anion channel termed VSOAC(volume-sensitive organic osmolyte/anion channel). Regulation of VSOACby intracellular electrolytes was characterized in Chinese hamsterovary cells by whole cell patch clamp. Elevation of intracellular CsClconcentration from 40 to 180 mM resulted in a concentration-dependentdecrease in channel activation. Activation of VSOAC was insensitive tothe salt gradient across the plasma membrane, the intracellularconcentration of specific anions or cations, and the totalintracellular concentration of cations, anions, or electrolytes.Comparison of cells dialyzed with either CsCl orNa₂SO₄solutions demonstrated directly that VSOAC activation is modulated byintracellular ionic strength(µ_i). The relative cell volumeat which VSOAC current activation was triggered, termed the channelvolume set point, decreased with decreasing ionic strength. Atµ_i = 0.04, VSOAC activationoccurred spontaneously in shrunken cells. The rate of VSOAC activationwas nearly 50-fold higher in cells withµ_i = 0.04 vs. those withµ_i = 0.18. We propose thatµ_i modulates the volume sensorresponsible for channel activation.