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PLoS One. 2009 Jul 8;4(7):e6168. doi: 10.1371/journal.pone.0006168.

Characterization of voltage-gated potassium channels in human neural progenitor cells.

Author information

  • 1Department of Neurology, University of Leipzig, Leipzig, Germany. grit.schaarschmidt@medizin.uni-leipzig.de

Abstract

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.

PMID:
19584922
[PubMed - indexed for MEDLINE]
PMCID:
PMC2702754
Free PMC Article
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