P-glycoprotein is Not a Swelling-activated Cl- Channel; Possible Role As a Cl- Channel Regulator

Overview

Journal J Physiol

Specialty Physiology

Date 1997 Jul 15

PMID 9263907

Citations 7

Authors

C G Vanoye

G A Altenberg

L Reuss

Affiliations

Soon will be listed here.

Abstract

1. The whole-cell configuration of the patch-clamp technique was used to determine if P-glycoprotein (Pgp) is a swelling-activated Cl- channel. 2. Hamster pgp1 cDNA was transfected into a mouse fibroblast cell line resulting in expression of functional Pgp in the plasma membrane. This cell line was obtained without exposure to chemotherapeutic agents. 3. Swelling-activated whole-cell Cl- current (ICl,swell) was elicited by lowering the bath osmolality. ICl,swell was characterized in detail in the pgp1-transfected mouse cell line and compared with that of its parental cell line. Expression of Pgp did not modify the magnitude or properties of ICl,swell, except that addition of the anti-Pgp antibody C219 to the pipette solution inhibited this current by 75% only in the Pgp-expressing cells. 4. ICl,swell in the mouse Pgp-expressing cell line was compared with that in a Pgp-expressing hamster fibroblast cell line. The characteristics of ICl,swell (voltage dependence, blocker sensitivity, anion selectivity sequence, requirement for hydrolysable ATP) in Pgp-expressing cells were different between the two cell lines. These results suggest that the channel(s) responsible for ICl,swell are different between the two cell lines. In addition, C219 inhibited ICl,swell in both Pgp-expressing cell lines, even though they seem to express different swelling-activated Cl- channels. 5. We conclude that firstly, Pgp is not a swelling-activated Cl- channel; secondly, it possibly functions as a Cl- channel regulator; and thirdly, ICl,swell is underlined by different Cl- channels in different cells.

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References

Yamashita N, Hamada H, Tsuruo T, Ogata E . Enhancement of voltage-gated Na+ channel current associated with multidrug resistance in human leukemia cells. Cancer Res. 1987; 47(14):3736-41. View

Schwiebert E, Egan M, Hwang T, Fulmer S, Allen S, Cutting G . CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell. 1995; 81(7):1063-73. DOI: 10.1016/s0092-8674(05)80011-x. View

Lindau M, Neher E . Patch-clamp techniques for time-resolved capacitance measurements in single cells. Pflugers Arch. 1988; 411(2):137-46. DOI: 10.1007/BF00582306. View

Hasmann M, Valet G, Tapiero H, Trevorrow K, Lampidis T . Membrane potential differences between adriamycin-sensitive and -resistant cells as measured by flow cytometry. Biochem Pharmacol. 1989; 38(2):305-12. DOI: 10.1016/0006-2952(89)90041-5. View

Hoffmann E, Simonsen L . Membrane mechanisms in volume and pH regulation in vertebrate cells. Physiol Rev. 1989; 69(2):315-82. DOI: 10.1152/physrev.1989.69.2.315. View

Georges E, Bradley G, Gariepy J, Ling V . Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. Proc Natl Acad Sci U S A. 1990; 87(1):152-6. PMC: 53218. DOI: 10.1073/pnas.87.1.152. View

Arias I . Multidrug resistance genes, p-glycoprotein and the liver. Hepatology. 1990; 12(1):159-65. DOI: 10.1002/hep.1840120125. View

Rich D, Anderson M, Gregory R, Cheng S, Paul S, Jefferson D . Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature. 1990; 347(6291):358-63. DOI: 10.1038/347358a0. View

Kartner N, Hanrahan J, Jensen T, Naismith A, Sun S, Ackerley C . Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductance. Cell. 1991; 64(4):681-91. DOI: 10.1016/0092-8674(91)90498-n. View

10.

Devine S, Hussain A, Davide J, Melera P . Full length and alternatively spliced pgp1 transcripts in multidrug-resistant Chinese hamster lung cells. J Biol Chem. 1991; 266(7):4545-55. View

11.

Bear C, Li C, Kartner N, Bridges R, Jensen T, Ramjeesingh M . Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR). Cell. 1992; 68(4):809-18. DOI: 10.1016/0092-8674(92)90155-6. View

12.

Valverde M, Diaz M, Sepulveda F, Gill D, Hyde S, Higgins C . Volume-regulated chloride channels associated with the human multidrug-resistance P-glycoprotein. Nature. 1992; 355(6363):830-3. DOI: 10.1038/355830a0. View

13.

McEwan G, Hunter J, Hirst B, Simmons N . Volume-activated Cl- secretion and transepithelial vinblastine secretion mediated by P-glycoprotein are not correlated in cultured human T84 intestinal epithelial layers. FEBS Lett. 1992; 304(2-3):233-6. DOI: 10.1016/0014-5793(92)80626-r. View

14.

Doige C, Sharom F . Transport properties of P-glycoprotein in plasma membrane vesicles from multidrug-resistant Chinese hamster ovary cells. Biochim Biophys Acta. 1992; 1109(2):161-71. DOI: 10.1016/0005-2736(92)90079-2. View

15.

Sognier M, Zhang Y, Eberle R, BELLI J . Characterization of adriamycin-resistant and radiation-sensitive Chinese hamster cell lines. Biochem Pharmacol. 1992; 44(9):1859-68. DOI: 10.1016/0006-2952(92)90082-t. View

16.

Altenberg G, Young G, Horton J, Glass D, BELLI J, Reuss L . Changes in intra- or extracellular pH do not mediate P-glycoprotein-dependent multidrug resistance. Proc Natl Acad Sci U S A. 1993; 90(20):9735-8. PMC: 47645. DOI: 10.1073/pnas.90.20.9735. View

17.

Altenberg G, Subramanyam M, Bergmann J, Johnson K, Reuss L . Muscarinic stimulation of gallbladder epithelium. I. Electrophysiology and signaling mechanisms. Am J Physiol. 1993; 265(6 Pt 1):C1604-12. DOI: 10.1152/ajpcell.1993.265.6.C1604. View

18.

Rasola A, Galietta L, Gruenert D, Romeo G . Volume-sensitive chloride currents in four epithelial cell lines are not directly correlated to the expression of the MDR-1 gene. J Biol Chem. 1994; 269(2):1432-6. View

19.

Luckie D, Krouse M, Harper K, Law T, Wine J . Selection for MDR1/P-glycoprotein enhances swelling-activated K+ and Cl- currents in NIH/3T3 cells. Am J Physiol. 1994; 267(2 Pt 1):C650-8. DOI: 10.1152/ajpcell.1994.267.2.C650. View

20.

Thevenod F, Anderie I, Schulz I . Monoclonal antibodies against MDR1 P-glycoprotein inhibit chloride conductance and label a 65-kDa protein in pancreatic zymogen granule membranes. J Biol Chem. 1994; 269(39):24410-7. View