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Author Notes:

Correspondence: Shan Ping Yu, M.D., Ph.D., 101 Woodruff Circle, Room 620, Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, 30322; Email: spyu@emory.edu


Research Funding:

This work was supported by NIH grants NS 045810 (LW), NS 058710 (LW), NS057255 (SPY) and the American Heart Association Established Investigator Award (LW).

This work was also supported by the NIH grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources at MUSC and the NIH grant NS055077 to the ENNCF (Emory Neurology-NINDS Core Facility).


  • M-current
  • synaptogenesis
  • Neuronal differentiation
  • Mouse ES cells
  • Hippocampal neurons
  • KCNQ channels
  • ERK1/2

Potential Role of KCNQ/M-Channels in Regulating Neuronal Differentiation in Mouse Hippocampal and Embryonic Stem Cell-Derived Neuronal Cultures


Journal Title:

Experimental Neurology


Volume 229, Number 2


, Pages 471-483

Type of Work:

Article | Post-print: After Peer Review


Voltage-gated K+ channels are key regulators of neuronal excitability, playing major roles in setting resting membrane potential, repolarizing the cell membrane after action potentials and affecting transmitter release. The M-type channel or M-channel is a unique voltage- and ligand-regulated K+ channel. It is composed of the molecular counterparts KCNQ2 and KCNQ3 (also named Kv7.2 and Kv7.3) channels and expressed in the soma and dendrites of neurons. The present investigation examined the hypothesis that KCNQ2/3 channels played a regulatory role in neuronal differentiation and maturation. In cultured mouse embryonic stem (ES) cells undergoing neuronal differentiation and primary embryonic (E15-17) hippocampal cultures, KCNQ2 and KCNQ3 channels and underlying M-currents were identified. Blocking of KCNQ channels in these cells for 5 days using the specific channel blocker XE991 (10 μM) or linopirdine (30 μM) significantly decreased synaptophysin and syntaxin expression without affecting cell viability. Chronic KCNQ2/3 channel block reduced the expression of vesicular GABA transporter (v-GAT), but not vesicular glutamate transporter (v-GluT). Enhanced ERK1/2 phosphorylation was observed in XE991- and linopirdine-treated neural progenitor cells. In electrophysiological recordings, cells undergoing chronic block of KCNQ2/3 channels showed normal amplitude of mPSCs while the frequency of mPSCs was reduced. On the other hand, KCNQ channel opener N-Ethylmaleimide (NEM, 2 μM) increased mPSC frequency. Fluorescent imaging using fluorescent styryl-dye FM4-64 revealed that chronic blockade of KCNQ2/3 channels decreased endocytosis but facilitated exocytosis. These data indicate that KCNQ2/3 channels participate in regulation of neuronal differentiation and show a tonic regulation on pre-synaptic transmitter release and recycling in developing neuronal cells.

Copyright information:

© 2011 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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