Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels

J Neurophysiol. 2016 Nov 1;116(5):2114-2124. doi: 10.1152/jn.00446.2016. Epub 2016 Aug 10.


KCNQ/Kv7 channels form a slow noninactivating K+ current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/Kv7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/Kv7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/Kv7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners.

Keywords: XE991; membrane properties; retigabine; spinal cord; voltage threshold.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Down-Regulation / drug effects
  • Down-Regulation / physiology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • KCNQ Potassium Channels / agonists
  • KCNQ Potassium Channels / antagonists & inhibitors
  • KCNQ Potassium Channels / physiology*
  • Mice
  • Motor Neurons / drug effects
  • Motor Neurons / physiology*
  • Organ Culture Techniques
  • Spinal Cord / drug effects
  • Spinal Cord / physiology*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • KCNQ Potassium Channels