Stefan Liebau, Christian Pro¨pper, Tobias Bo¨ckers, Frank Lehmann-Horn, Alexander Storch,
Stephan Grissmer and Oliver H. Wittekindt
Abstract
The modulation of cell proliferation in neural progenitor cells
(NPCs) is believed to play a role in neuronal regeneration.
Recent studies showed that K+ channel activity influenced cell
proliferation. Therefore, we examined NPCs for K+ channels
and tested whether NPC self renewing can be modulated by
synthetic K+ channel modulators. The whole-cell K+ current
was partly K+ dependent and showed a cumulative inactivating
component. Two tetra-ethyl-ammonium ion (TEA)-sensitve
K+ currents with different voltage dependencies (IC1
50 ¼
65 lM, E50 ¼ )0.3 ± 1.3 mV and IC2
50 ¼ 8 mM, E50 ¼
)15.2 ± 2.8 mV) and an almost TEA-insensitive current were
identified. Kaliotoxin blocked approximately 50% of the entire
K+ currents (IC50 ¼ 0.25 nM). These properties resembled
functional characteristics of Kv1.4, Kv1.3 and Kv3.1 channels.
Transcripts for these channels, as well as proteins for Kv1.3
and Kv3.1, were identified. Immunocytochemical staining
revealed Kv1.3 and Kv3.1 K+ channel expression in almost all
NPCs. The blockage of Kv3.1 by low concentrations of TEA,
as well as the blockage of Kv1.3 by Psora-4, increased NPC
proliferation. These findings underline the regulatory role of K+
channels on the cell cycle and imply that K+ channel modulators
might be used therapeutically to activate endogenous
NPCs.