Ionic strength regulates volume sensitivity of the swelling-activated anion conductance I-Cl swell.
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Regulation of ICl,swell by intracellular electrolytes was characterized by whole cell patch clamp in Chinese hamster ovary cells. Electrolyte concentrations were altered by isosmotic substitution of CsCl in patch pipette solutions with sucrose. Elevation of salt concentration [s] from 40 to 180 mM resulted in a concentration-dependent decrease in ICl,swell activation. Current activation was insensitive to intracellular [sucrose] and extracellular [s]. Substitution of Cl- or Cs+ with various monovalent anions and cations had no effect on current activation. Thus, ICl,swell activation appeared to be sensitive to either total cation [c] or anion concentrations [a], total [s] or intracellular ionic strength (i). To determine which parameter was important for channel regulation, i was held constant and [c], [a] and [s] were varied simultaneously by replacement of CsCl with Na2SO4. Current activation was the same in cells dialyzed with either CsCl or Na2SO4 solutions that had identical ionic strength. These findings demonstrate that ICl,swell is regulated by i rather than [c], [a] or [s]. Intracellular altered the volume sensitivity of the ICl,swell channel. The amount of cell swelling required to initiate current activation, termed the volume set-point, decreased with decreasing i. At i = 0.04, ICl,swell activated spontaneously in cells shrunken 15-20%. The rate of ICl,swell activation was nearly 50 fold higher in cells with i, = 0.04 versus i = 0.18. We propose that i modulates the volume sensor responsible for activation of ICl,swell. Given the postulated role of the ICl,swell channel in organic osmolyte efflux, its regulation by i may provide cells with a mechanism to simultaneously control their volume, organic osmolyte levels and electrolyte composition.