title: Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons.
abstract: 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.
authors.affiliation: Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. lawrenjo@mail.nih.gov
authors.forename: J Josh
authors.initials: JJ
authors.lastname: Lawrence
authors.forename: Fernanda
authors.initials: F
authors.lastname: Saraga
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Churchill
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Statland
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Travis
authors.forename: Frances K
authors.initials: FK
authors.lastname: Skinner
authors.forename: Chris J
authors.initials: CJ
authors.lastname: McBain
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002460:Cell Line; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007395:Interneurons / Q000502:physiology*; D051656:KCNQ Potassium Channels / Q000145:classification / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D018408:Patch-Clamp Techniques / Q000379:methods; D010655:Phenylenediamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014162:Transfection / Q000379:methods
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D002219:Carbamates; D007211:Indoles; D051656:KCNQ Potassium Channels; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D011725:Pyridines; C101866:ezogabine; D049452:Green Fluorescent Proteins; D019789:Tetraethylammonium; C061017:linopirdine