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P-Glycoprotein-associated Cl^- Currents Are Activated by Cell Swelling but Do Not Contribute to Cell Volume Regulation¹

Department of Physiology and Biophysics, The University of Texas Medical Branch, Galveston, Texas 77555-0641

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.

¹ This work was supported in part by a grant from the John Sealy Memorial Endowment Fund. Mr. C. G. Vanoye was supported by NIH Grant DK08865.

² Present address: Department of Zoology, FB Biologie, Postfach 3049, Universität Kaiserslautern, D-6750 Kaiserslautern, Germany.

³ To whom reprint requests should be addressed, at: Department of Physiology and Biophysics, The University of Texas Medical Branch, Basic Science Bldg., Galveston, TX 77555-0641.

Received 10/ 1/93. Accepted 12/16/93.

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