Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Am J Physiol Cell Physiol 267: C650-C658, 1994;
0363-6143/94 $5.00
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luckie, D. B.
Right arrow Articles by Wine, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luckie, D. B.
Right arrow Articles by Wine, J. J.

AJP - Cell Physiology, Vol 267, Issue 2 C650-C658, Copyright © 1994 by American Physiological Society


ARTICLES

Selection for MDR1/P-glycoprotein enhances swelling-activated K+ and Cl- currents in NIH/3T3 cells

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:


Home page
J. Neurophysiol.Home page
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]


Home page
Physiol. Rev.Home page
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]


Home page
Am. J. Physiol. Cell Physiol.Home page
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]


Home page
J. Biol. Chem.Home page
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