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Inwardly Rectifying K⁺ Channels and Volume-regulated Anion Channels in Multidrug-resistant Small Cell Lung Cancer Cells¹

Department of Physiology [J. J., D. F.] and the Cancer Research Laboratories [R. G. D., S. P. C. C., A. J. S.], Queen's University, Kingston, Canada K7L 3N6

Studies of multidrug-resistant H69AR cells which overexpress the multidrug resistance-associated protein, compared with drug-sensitive parental H69 cells and revertant H69PR cells, revealed an inwardly rectifying K⁺ channel current (conductance, 231 pS/pF) and increased volume-regulated anion current (limiting conductance, 2 nS/pF). The anion current was selective for Cl^- ions and sensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (0.1–1 mM) but ATP was not required for initial current activation even in excised patch experiments. K⁺ current reversal potential varied 52 mV/10-fold change in the external K⁺ concentration and current was blocked by BaCl₂ (0.1–1 mM). The results indicate that overexpression of multidrug resistance-associated protein is accompanied by increases in both K⁺ channel and volume-regulated Cl^- channel current in the multidrug-resistant cell line H69AR.

¹ Supported by grants from the Heart and Stroke Foundation of Ontario (D. F.), the Medical Research Council of Canada (R. G. D., S. P. C. C., D. F.), and the National Cancer Institute of Canada (S. P. C.C.). A. J. S. is the recipient of a postdoctoral fellowship from the Cancer Research Society. S. P. C. C. is a Career Scientist of the Ontario Cancer Treatment and Research Foundation, and R. G. D. is the Queen's University Stauffer Research Professor of basic cancer research. D. F. is a Research Scholar of the Heart and Stroke Foundation of Ontario.

² To whom requests for reprints should be addressed.

Received 5/19/93. Accepted 8/ 3/93.

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