Voltage-independent sodium channels emerge for an expression of activity-induced spontaneous spikes in GABAergic neurons

Mol Brain. 2014 May 20;7:38. doi: 10.1186/1756-6606-7-38.


Background: Cerebral overexcitation needs inhibitory neurons be functionally upregulated to rebalance excitation vs. inhibition. For example, the intensive activities of GABAergic neurons induce spontaneous spikes, i.e., activity-induced spontaneous spikes (AISS). The mechanisms underlying AISS onset remain unclear. We investigated the roles of sodium channels in AISS induction and expression at hippocampal GABAergic neurons by electrophysiological approach.

Results: AISS expression includes additional spike capability above evoked spikes, and the full spikes in AISS comprise early phase (spikelets) and late phase, implying the emergence of new spikelet component. Compared with the late phase, the early phase is characterized as voltage-independent onset, less voltage-dependent upstroke and sensitivity to TTX. AISS expression and induction are independent of membrane potential changes. Therefore, AISS's spikelets express based on voltage-independent sodium channels. In terms of AISS induction, the facilitation of voltage-gated sodium channel (VGSC) activation accelerates AISS onset, or vice versa.

Conclusion: AISS expression in GABAergic neurons is triggered by the spikelets based on the functional emergence of voltage-independent sodium channels, which is driven by intensive VGSCs' activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Arachidonic Acids / pharmacology
  • Axons / drug effects
  • Axons / physiology
  • Calcium Channels / metabolism
  • Cnidarian Venoms / toxicity
  • Endocannabinoids / pharmacology
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / physiology*
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Mice
  • Mice, Inbred C57BL
  • Polyunsaturated Alkamides / pharmacology
  • Sodium Channels / metabolism*
  • Tetrodotoxin / toxicity


  • Arachidonic Acids
  • Calcium Channels
  • Cnidarian Venoms
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Sodium Channels
  • Tetrodotoxin
  • toxin II (Anemonia sulcata)
  • anandamide