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


RESULTS
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
These findings suggest that A-type potassium currents are essential for proper proliferation of immature multipotent hNPCs.
Schaarschmidt
Grit
G
Department of Neurology, University of Leipzig, Leipzig, Germany. grit.schaarschmidt@medizin.uni-leipzig.de
Wegner
Florian
F
Schwarz
Sigrid C
SC
Schmidt
Hartmut
H
Schwarz
Johannes
J
D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*
D026902:Potassium Channel Blockers; D015221:Potassium Channels