Comparison of ion channels in multidrug-resistant and -sensitive human leukemic cells

Abstract

Tumor cell lines selected to grow in the presence of one "natural product" antineoplastic drug often develop cross-resistance to others. This multidrug resistance (MDR) is believed to be a major problem in cancer therapy. Organic Ca2+-channel blockers, such as verapamil, can reverse this resistance and render MDR cells in culture nearly as sensitive to the antineoplastic drugs as the drug-sensitive cells from which they were derived. It has therefore been suggested that Ca2+ channels may play a role in MDR. To determine directly whether there are electrophysiological correlates of MDR, we used whole-cell and single-channel patch-clamp techniques to survey the ion channels in a drug-sensitive human T-cell leukemia line, CCRF-CEM, and a MDR variant, CEM/VLB100. We found no evidence for a voltage-gated Ca2+ channel. However, we did identify three other current/channel types: a voltage-gated tetrodotoxin-sensitive inward current carried by Na+, a voltage-gated labile outward current carried by K+, and a nonselective cation channel reversing at 0 mV. Drug-sensitive and -resistant cells were the same with respect to the level of expression of these channels.