Selective blockage of Kv1.3 and Kv3.1 channels increases neural progenitor cell proliferation.
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)-sensitive K(+) currents with different voltage dependencies ( = 65 microm, E(50) = -0.3 +/- 1.3 mV and = 8 mm, E(50) = -15.2 +/- 2.8 mV) and an almost TEA-insensitive current were identified. Kaliotoxin blocked approximately 50% of the entire K(+) currents (IC(50) = 0.25 nm). These properties resembled functional characteristics of K(v)1.4, K(v)1.3 and K(v)3.1 channels. Transcripts for these channels, as well as proteins for K(v)1.3 and K(v)3.1, were identified. Immunocytochemical staining revealed K(v)1.3 and K(v)3.1 K(+) channel expression in almost all NPCs. The blockage of K(v)3.1 by low concentrations of TEA, as well as the blockage of K(v)1.3 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.
Liebau
Stefan
S
Department of Anatomy and Cell Biology, University of Ulm, Ulm, Germany.
Pröpper
Christian
C
Böckers
Tobias
T
Lehmann-Horn
Frank
F
Storch
Alexander
A
Grissmer
Stephan
S
Wittekindt
Oliver H
OH
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008636:Mesencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology; D051670:Shaw Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology
D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D012604:Scorpion Venoms; D051670:Shaw Potassium Channels; C072276:kaliotoxin; D019789:Tetraethylammonium