P-GLYCOPROTEIN-ASSOCIATED CHLORIDE CURRENTS REVEALED BY SPECIFIC BLOCK BY AN ANTI-P-GLYCOPROTEIN ANTIBODY

The relationships between P-glycoprotein (PGP) expression and plasma m embrane ion currents activated by cell swelling were studied in severa l cell lines by use of the whole cell configuration of the patch-clamp technique. Swelling-activated Cl- currents (I-Cl(S)) had similar char acteristics independently of whether PGP was expressed. Addition of th e anti-PGP monoclonal antibody C219 or its Fab fragment to the pipette solution prevented I-Cl(S) in cells expressing functional PGP (assess ed by immunoblots, immunofluorescence, and transport of rhodamine 123) but not in cells lacking PGP expression. A peptide analogue of the C2 19 epitope abolished the effect of C219. Other anti-POP antibodies and mouse immunoglobulin G were ineffective. C219 did not alter swelling- activated cation currents. Inasmuch as I-Cl(S) is present in cells tha t do not express PGP and C219 has no effect on I-Cl(S) in these cells, we conclude that PGP is not required for the I-Cl(S) phenotype. Howev er, when expressed in the plasma membrane, PGP is involved, directly o r indirectly, in I-Cl(S) but not in swelling-activated K+ currents.