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 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.