title: Complementary functions of SK and Kv7/M potassium channels in excitability control and synaptic integration in rat hippocampal dentate granule cells.
abstract: The dentate granule cells (DGCs) form the most numerous neuron population of the hippocampal memory system, and its gateway for cortical input. Yet, we have only limited knowledge of the intrinsic membrane properties that shape their responses. Since SK and Kv7/M potassium channels are key mechanisms of neuronal spiking and excitability control, afterhyperpolarizations (AHPs) and synaptic integration, we studied their functions in DGCs. The specific SK channel blockers apamin or scyllatoxin increased spike frequency (excitability), reduced early spike frequency adaptation, fully blocked the medium-duration AHP (mAHP) after a single spike or spike train, and increased postsynaptic EPSP summation after spiking, but had no effect on input resistance (Rinput) or spike threshold. In contrast, blockade of Kv7/M channels by XE991 increased Rinput, lowered the spike threshold, and increased excitability, postsynaptic EPSP summation, and EPSP-spike coupling, but only slightly reduced mAHP after spike trains (and not after single spikes). The SK and Kv7/M channel openers 1-EBIO and retigabine, respectively, had effects opposite to the blockers. Computational modelling reproduced many of these effects. We conclude that SK and Kv7/M channels have complementary roles in DGCs. These mechanisms may be important for the dentate network function, as CA3 neurons can be activated or inhibition recruited depending on DGC firing rate.
authors.affiliation: Department of Physiology, IMB, University of Oslo, PB 1104 Blindern, 0317 Oslo, Norway.  j.f.storm@medisin.uio.no.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mateos-Aparicio
authors.forename: Ricardo
authors.initials: R
authors.lastname: Murphy
authors.forename: Johan F
authors.initials: JF
authors.lastname: Storm
mesh_terms: D000200:Action Potentials; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010655:Phenylenediamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D051656:KCNQ Potassium Channels; D049990:Membrane Transport Modulators; D010655:Phenylenediamines; D051640:Small-Conductance Calcium-Activated Potassium Channels; C101866:ezogabine; C102635:1-ethyl-2-benzimidazolinone