P-GLYCOPROTEIN-ASSOCIATED CL- CURRENTS ARE ACTIVATED BY CELL SWELLINGBUT DO NOT CONTRIBUTE TO CELL-VOLUME REGULATION

P-glycoprotein-associated Cl- conductance is activated by cell swellin g; the ensuing Cl- efflux is thought to contribute to cell volume regu lation. We tested this hypothesis in human breast cancer cells transfe cted with human mdr1 complementary DNA, which display P-glycoprotein-a ssociated, swelling-activated Cl- currents. The Cl- electrochemical dr iving force favors Cl- efflux, but there was no appreciable Cl- loss o r regulatory volume decrease (both assessed with fluorescent dyes) dur ing the exposure to hyposmotic solution. Calculations indicate that th e swelling-activated Cl- current is insufficient to cause a significan t Cl- efflux. Hence, regulatory volume decrease is not a function of P -glycoprotein.