Macrophage-colony-stimulating factor (CSF-1) modulates a differentiation-specific inward-rectifying potassium current in human leukemic (HL-60) cells.
A voltage-activated inward-rectifying K+ conductance (lKi) appears in human promyelocytic leukemia (HL-60) cells during phorbol ester-induced differentiation into macrophages. This conductance was detected in the cells 24 hours after exposure to phorbol-12-myristate-13-acetate (PMA), as the cells began to express the macrophage phenotype, and continued to increase for 4 days after PMA exposure. The magnitude of inward current was a function of external K+; current was blocked by extracellular or intracellular Cs+ and by extracellular Ba++. Hyperpolarization produced activation at membrane potentials more negative than -80 mV, and a slower, partial inactivation also occurred at potentials more negative than -100 mV. This conductance was not detected in proliferating cells nor in granulocytes derived from HL-60 cells which were induced to differentiate with retinoic acid (RA). Exposure of differentiated macrophages to recombinant human CSF-1 produced inhibition of the lKi beginning within 1 minute after exposure. CSF-1 inhibition of lKi channels in cell-attached patches indicated that channel modulation was via intracellular mediators. The rapid inhibition of the inward rectifier by the macrophage-specific CSF-1 appears to be one of the earliest cellular responses to this factor.
Wieland
S J
SJ
Department of Anatomy, Hahnemann University, Philadelphia, Pennsylvania 19102.
Chou
R H
RH
Gong
Q H
QH
D002454:Cell Differentiation / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004553:Electric Conductivity; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D015221:Potassium Channels; D016173:Macrophage Colony-Stimulating Factor; D011188:Potassium