Selection for MDR1/P-glycoprotein enhances swelling-activated K+ and Cl- currents in NIH/3T3 cells
| Autor: | Douglas B. Luckie, Jeffrey J. Wine, Mauri E. Krouse, T. C. Law, K. L. Harper |
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| Rok vydání: | 1994 |
| Předmět: |
Anions
Serial dilution Physiology Analytical chemistry 3T3 cells Cell Line Mice Chlorides medicine Animals Edema ATP Binding Cassette Transporter Subfamily B Member 1 P-glycoprotein Membrane Glycoproteins biology Chemistry Electric Conductivity Conductance 3T3 Cells Cell Biology Fibroblasts Potassium channel Electrophysiology medicine.anatomical_structure Hypotonic Solutions Cell culture Potassium Biophysics biology.protein Verapamil Efflux Carrier Proteins Colchicine medicine.drug |
| Zdroj: | American Journal of Physiology-Cell Physiology. 267:C650-C658 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1994.267.2.c650 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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