P-glycoprotein-associated Cl- currents are activated by cell swelling but do not contribute to cell volume regulation.

P-glycoprotein-associated Cl- conductance is activated by cell swelling; the ensuing Cl- efflux is thought to contribute to cell volume regulation. We tested this hypothesis in human breast cancer cells transfected with human mdr1 complementary DNA, which display P-glycoprotein-associated, swelling-activated Cl- currents. The Cl- electrochemical driving force favors Cl- efflux, but there was no appreciable Cl- loss or regulatory volume decrease (both assessed with fluorescent dyes) during the exposure to hyposmotic solution. Calculations indicate that the swelling-activated Cl- current is insufficient to cause a significant Cl- efflux. Hence, regulatory volume decrease is not a function of P-glycoprotein.