Abstract
Primitive human hemopoietic progenitor cells identified by surface membrane markers CD33−CD34+ are capable of expansion into lineage-restricted precursors following in vitro stimulation by hemopoietic regulators such as stem cell factor (SCF) and interleukin-3 (IL-3). In search of ionic currents involved in cytokine-induced progenitor cell growth and differentiation, human umbilical cord blood CD33−CD34+ cells were subjected to perforated patch-clamp recordings following overnight incubation with SCF and/or IL-3. An inward rectifying potassium channel (Kir) was found in 33% of control unstimulated cells, in 34% of cells incubated with IL-3, in 31 % of cells incubated with SCF and in 75% of cells incubated with IL-3 plus SCE Kir activity increased with elevation of extracellular potassium and was blocked by extracellular Cs+ or Ba2+. Antisense oligodeoxynucleotides directed against Kir blocked both mRNA and functional expression of Kir channels. Kir antisense also inhibited the in vitro expansion of cytokine-stimulated CD33−CD34+ cells into erythroid (BFU-E) and myeloid (GM-CFU) progenitors in 7-day suspension cultures. Extracellular Cs+ or Ba2+ induced a similar degree of inhibition (40–60%) of progenitor cell generation. These findings strongly suggest an essential role for Kir in the process of cytokine-induced primitive progenitor cell growth and differentiation.
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Shirihai, O., Merchav, S., Attali, B. et al. K+ channel antisense oligodeoxynucleotides inhibit cytokine-induced expansion of human hemopoietic progenitors. Pflugers Arch. 431, 632–638 (1996). https://doi.org/10.1007/BF02191913
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DOI: https://doi.org/10.1007/BF02191913