P-glycoprotein-associated chloride currents revealed by specific block by an anti-P-glycoprotein antibody

Ernest S. Han, Carlos G. Vanoye, Guillermo A. Altenberg, Luis Reuss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The relationships between P-glycoprotein (PGP) expression and plasma membrane ion currents activated by cell swelling were studied in several cell lines by use of the whole cell configuration of the patch-clamp technique. Swelling-activated Cl currents (I(Cl)/(s)) had similar characteristics independently of whether PGP was expressed. Addition of the anti-PGP monoclonal antibody C219 or its Fab fragment to the pipette solution prevented I(Cl)/(s) in cells expressing functional PGP (assessed by immunoblots, immunofluorescence, and transport of rhodamine 123) but not in cells lacking PGP expression. A peptide analogue of the C219 epitope abolished the effect of C219. Other anti-PGP antibodies and mouse immunoglobulin G were ineffective. C219 did not alter swelling-activated cation currents. Inasmuch as I(Cl)/(s) is present in cells that 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. However, when expressed in the plasma membrane, PGP is involved, directly or indirectly, in I(Cl)/(s) but not in swelling-activated K+ currents.

Original languageEnglish (US)
Pages (from-to)C1370-C1378
JournalAmerican Journal of Physiology - Cell Physiology
Volume270
Issue number5 39-5
DOIs
StatePublished - May 1996

Keywords

  • C219
  • MCF-7
  • cell volume regulation
  • chloride channels
  • multidrug resistance
  • rhodamine 123

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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