|
|
||||||||
AJP - Cell Physiology, Vol 267, Issue 2 C650-C658, Copyright © 1994 by American Physiological Society
ARTICLES |
D. B. Luckie, M. E. Krouse, K. L. Harper, T. C. Law and J. J. Wine
Cystic Fibrosis Research Laboratory, Stanford University, California 94305-2130.
The relationship between multidrug resistance (MDR) P-glycoprotein expression and swelling-activated Cl- and K+ conductance was investigated in mouse NIH/3T3 fibroblasts and their colchicine-selected counterparts (COL1000, high P-glycoprotein). Whole cell patch-clamp and isotopic flux experiments confirmed that swelling-activated Cl- currents were induced by 20-30% bath dilution only in the MDR-expressing cell line. However, at bath dilutions > 30%, both cell lines developed Cl- currents that reached similar large magnitudes at higher dilution levels. Thus the apparent absolute difference in cell lines at lower dilutions is due to a shift in the response curve relating hypotonicity to Cl- conductance. At all dilutions and in both cell lines, the swelling-activated Cl- currents were outwardly rectifying, active at negative cell voltages, and inactivated at positive voltages. Verapamil (100 microM) and 1,9-dideoxyforskolin (100 microM), which inhibit P-glycoprotein drug transport, did not significantly inhibit the swelling-activated Cl- conductance efflux in the COL1000 cells also showed a leftward shift in the response curve to hypotonicity. These results indicate that response curve to hypotonicity. These results indicate that colchicine-selection for increased P-glycoprotein expression did not lead to the expression of swelling-activated Cl- channels, but instead enhanced a step in the pathway from bath dilution to regulatory volume decrease that is common to both K+ and Cl- channels.
This article has been cited by other articles:
![]() |
M. Darby, J. B. Kuzmiski, W. Panenka, D. Feighan, and B. A. MacVicar ATP Released From Astrocytes During Swelling Activates Chloride Channels J Neurophysiol, April 1, 2003; 89(4): 1870 - 1877. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Hume, D. Duan, M. L. Collier, J. Yamazaki, and B. Horowitz Anion Transport in Heart Physiol Rev, January 1, 2000; 80(1): 31 - 81. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. G. Vanoye, A. F. Castro, T. Pourcher, L. Reuss, and G. A. Altenberg Phosphorylation of P-glycoprotein by PKA and PKC modulates swelling-activated Cl- currents Am J Physiol Cell Physiol, February 1, 1999; 276(2): C370 - C378. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Roman, Y. Wang, S. D. Lidofsky, A. P. Feranchak, N. Lomri, B. F. Scharschmidt, and J. G. Fitz Hepatocellular ATP-binding Cassette Protein Expression Enhances ATP Release and Autocrine Regulation of Cell Volume J. Biol. Chem., August 29, 1997; 272(35): 21970 - 21976. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |