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.
Altenberg
G A
GA
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555-0641.
Deitmer
J W
JW
Glass
D C
DC
Reuss
L
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000502:physiology*; D002463:Cell Membrane Permeability; D048429:Cell Size / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism / Q000493:pharmacokinetics; D004351:Drug Resistance; D004563:Electrochemistry; D005260:Female; D006801:Humans; D007038:Hypotonic Solutions; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D018118:Chloride Channels; D002712:Chlorides; D007038:Hypotonic Solutions; D008562:Membrane Glycoproteins; D011188:Potassium