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

Abstract 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 BaCl 2 (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.