tetrodotoxin and Leukemia--Myeloid

Patch clamp method was used to search for, and characterize ion channel activity which may participate in cation influx in human myeloid K562 cells. In cell-attached, outside-out and whole-cell experiments two types of voltage-insensitive Na-permeable channels were identified with different selectivities for monovalent cations, referred to as channels of high (HS) and low (LS) selectivity. The unitary conductance was similar for both channel types being 12 pS (145 mmol/l Na, 23 degrees C). The relative permeability PNa/PK estimated from the extrapolated reversal potential values were 10 and 3 for HS and LS channels, respectively. Both HS and LS channels were found to be impermeable to bivalent cations (Ca2+ or Ba2+). The activity of HS and LS channels displayed a tendency to increase with depolarization. Both channel types were not blocked by tetrodotoxin and were insensitive to amiloride in the concentration range of up to 100 mumol/l. At higher concentrations (0.1-2 mmol/l), amiloride reversibly inhibited HS channels only. The results obtained lead us to conclude that, under physiological conditions, both types of Na-permeable channels may provide sodium influx in leukemic cells. Our data imply the existence of a novel family of Na channels in blood cells.

Topics: Amiloride; Barium; Calcium; Cell Membrane; Cell Membrane Permeability; Diuretics; Humans; Ion Channel Gating; Leukemia, Myeloid; Patch-Clamp Techniques; Sodium Channels; Tetrodotoxin; Tumor Cells, Cultured