| 19584922 |
Schaarschmidt G, Wegner F, Schwarz SC, Schmidt H, Schwarz J: Characterization of voltage-gated potassium channels in human neural progenitor cells. PLoS One. 2009 Jul 8;4(7):e6168.
BACKGROUND: Voltage-gated potassium (K (v)) channels are among the earliest ion channels to appear during brain development, suggesting a functional requirement for progenitor cell proliferation and/or differentiation. We tested this hypothesis, using human neural progenitor cells (hNPCs) as a model system. METHODOLOGY/PRINCIPAL FINDINGS: In proliferating hNPCs a broad spectrum of K (v) channel subtypes was identified using quantitative real-time PCR with a predominant expression of the A-type channel K (v) 4.2. In whole-cell patch-clamp recordings K (v) currents were separated into a large transient component characteristic for fast-inactivating A-type potassium channels (I (A)) and a small, sustained component produced by delayed-rectifying channels (I (K)). During differentiation the expression of I (A) as well as A-type channel transcripts dramatically decreased, while I (K) producing delayed-rectifiers were upregulated. Both K (v) currents were differentially inhibited by selective neurotoxins like phrixotoxin-1 and alpha-dendrotoxin as well as by antagonists like 4-aminopyridine, ammoniumchloride, tetraethylammonium chloride and quinidine. In viability and proliferation assays chronic inhibition of the A-type currents severely disturbed the cell cycle and precluded proper hNPC proliferation, while the blockade of delayed-rectifiers by alpha-dendrotoxin increased proliferation. CONCLUSIONS/SIGNIFICANCE: These findings suggest that A-type potassium currents are essential for proper proliferation of immature multipotent hNPCs. |
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