Comparison of ion channels in multidrug-resistant and -sensitive human leukemic cells.
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.
D000970:Antineoplastic Agents / Q000627:therapeutic use; D004351:Drug Resistance; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000032:analysis*; D007938:Leukemia / Q000188:drug therapy*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D007473:Ion Channels; D012964:Sodium; D014700:Verapamil; D011188:Potassium