Educational Forum with Clinical Studies Current Science and Research

December 2, 2009

Selective blockage of Kv1.3 and Kv3.1 channels increases neural progenitor cell proliferation

Filed under: Xanya Sofra Weiss — Tags: — Dr. Xanya @ 1:08 am

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.

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