Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons

J Neurosci. 2006 Nov 22;26(47):12325-38. doi: 10.1523/JNEUROSCI.3521-06.2006.


The M-current (I(M)), comprised of Kv7 channels, is a voltage-activated K+ conductance that plays a key role in the control of cell excitability. In hippocampal principal cells, I(M) controls action potential (AP) accommodation and contributes to the medium-duration afterhyperpolarization, but the role of I(M) in control of interneuron excitability remains unclear. Here, we investigated I(M) in hippocampal stratum oriens (SO) interneurons, both from wild-type and transgenic mice in which green fluorescent protein (GFP) was expressed in somatostatin-containing interneurons. Somatodendritic expression of Kv7.2 or Kv7.3 subunits was colocalized in a subset of GFP+ SO interneurons, corresponding to oriens-lacunosum moleculare (O-LM) cells. Under voltage clamp (VC) conditions at -30 mV, the Kv7 channel antagonists linopirdine/XE-991 abolished the I(M) amplitude present during relaxation from -30 to -50 mV and reduced the holding current (I(hold)). In addition, 0.5 mM tetraethylammonium reduced I(M), suggesting that I(M) was composed of Kv7.2-containing channels. In contrast, the Kv7 channel opener retigabine increased I(M) amplitude and I(hold). When strongly depolarized in VC, the linopirdine-sensitive outward current activated rapidly and comprised up to 20% of the total current. In current-clamp recordings from GFP+ SO cells, linopirdine induced depolarization and increased AP frequency, whereas retigabine induced hyperpolarization and arrested firing. In multicompartment O-LM interneuron models that incorporated I(M), somatodendritic placement of Kv7 channels best reproduced experimentally measured I(M). The models suggest that Kv3- and Kv7-mediated channels both rapidly activate during single APs; however, Kv3 channels control rapid repolarization of the AP, whereas Kv7 channels primarily control the interspike interval.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Anthracenes / pharmacology
  • Carbamates / pharmacology
  • Cell Line
  • Computer Simulation
  • Dendrites / physiology*
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology*
  • Humans
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Indoles / pharmacology
  • Interneurons / physiology*
  • KCNQ Potassium Channels / classification
  • KCNQ Potassium Channels / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Transgenic
  • Models, Neurological
  • Patch-Clamp Techniques / methods
  • Phenylenediamines / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Pyridines / pharmacology
  • Tetraethylammonium / pharmacology
  • Transfection / methods


  • 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone
  • Anthracenes
  • Carbamates
  • Indoles
  • KCNQ Potassium Channels
  • Phenylenediamines
  • Potassium Channel Blockers
  • Pyridines
  • ezogabine
  • Green Fluorescent Proteins
  • Tetraethylammonium
  • linopirdine