Regulation of swelling-activated Cl- channels by P-glycoprotein (Pgp)

C. G. Vanoye*, A. F. Castro, G. A. Altenberg, L. Reuss

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Expression of Pgp could affect the functions of several transporters. Previous studies have shown a specific relationship between Pgp and swelling-activated Cl- currents (Cls), and suggested that Pgp is a Cl- channel regulator (EMBO J., 14:68-75; Am. J. Physiol., 270:C1370-C1378). Activation of protein kinase C (PKC) inhibits ICls only in Pgp-expressing cells. In these cells, Pgp expression was obtained by transfection and subsequent selection with chemotherapeutic agents or using a vaccinia virus expression system. Here, we report that activation of PKC with phorbol 12-myristate 13-acetate (PMA) inhibits ICls in cells transfected with Pgp cDNA, and selected without exposure to chemotherapeutic agents. In Pgp(+) cells, PMA (200 nM, 5 min prior to cell patch-clamp) reduced ICls from 208 ± 31 to 107 ± 28 pA/pF (all ICls values listed were measured at + 80 mV). Exposure of the Pgp(-) parental cells to PMA did not alter ICls. In a Pgp mutant in which serines 661, 667 and 671 were substituted by alanines, PMA had no effect: 262 ± 52 without PMA, and 260 ± 26 pA/pF with PMA. In Pgp(+) cells, 8-Br-cAMP reduced ICls from 254 ± 22 to 109 ± 3 pA/pF. These results, in conjunction with observations in cells expressing CFTR and the sulfonylurea receptor, suggest that phosphorylation of ABC proteins may be a widespread mechanism of regulation of membrane transporters.

Original languageEnglish (US)
Pages (from-to)A304
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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