Enhancement of voltage-gated Na+ channel current associated with multidrug resistance in human leukemia cells.

Membrane currents were examined in a drug-sensitive human leukemia cell line (K562) and its multidrug-resistant cell line (K562/ADM) under the whole-cell variation of the patch electrode voltage clamp technique. Most K562 cells showed only the outward current, which was completely suppressed by internal Cs+ ions and 20 mM ethyleneglycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In contrast to K562 cells, most K562/ADM cells showed tetrodotoxin-sensitive, voltage-gated Na+ channel current in addition to the outward current. Na+ current was observed in four of 29 K562 cells examined, while it was observed in 29 of 33 K562/ADM cells. Two revertant cell lines (R1-3, R1-5) did not show Na+ current. It was concluded that the amplitude of voltage-gated Na+ current increases in association with multidrug resistance in human leukemia cells.