RT Journal Article SR Electronic T1 Somatodendritic Kv7/KCNQ/M Channels Control Interspike Interval in Hippocampal Interneurons JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 12325 OP 12338 DO 10.1523/JNEUROSCI.3521-06.2006 VO 26 IS 47 A1 J. Josh Lawrence A1 Fernanda Saraga A1 Joseph F. Churchill A1 Jeffrey M. Statland A1 Katherine E. Travis A1 Frances K. Skinner A1 Chris J. McBain YR 2006 UL http://www.jneurosci.org/content/26/47/12325.abstract AB The M-current (IM), 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, IM controls action potential (AP) accommodation and contributes to the medium-duration afterhyperpolarization, but the role of IM in control of interneuron excitability remains unclear. Here, we investigated IM 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 IM amplitude present during relaxation from −30 to −50 mV and reduced the holding current (Ihold). In addition, 0.5 mm tetraethylammonium reduced IM, suggesting that IM was composed of Kv7.2-containing channels. In contrast, the Kv7 channel opener retigabine increased IM amplitude and Ihold. 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 IM, somatodendritic placement of Kv7 channels best reproduced experimentally measured IM. 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.