title: Network excitability in a model of chronic temporal lobe epilepsy critically depends on SK channel-mediated AHP currents.
abstract: Hippocampal CA1 pyramidal neurons generate an after-hyperpolarization (AHP) whose medium component is thought to be generated by small-conductance Ca(2+)-activated K(+) channels (SK channels). Neuronal excitability is increased in epilepsy, and the AHP in turn is fundamentally involved in regulation of cellular excitability. We therefore investigated the involvement of the SK channel-mediated AHP in controlling cell and network excitability in the pilocarpine model epilepsy. Both acutely isolated CA1 pyramidal cells and isolated hippocampal slices were investigated in terms of the impact of SK channel-mediated AHP on hyperexcitability. Our findings show that pilocarpine-treated chronically epileptic rats exhibit significantly reduced SK channel-mediated hyperpolarizing outward current which was accompanied by a significant decrease in the somatic AHP. Paradoxically, inhibiting SK channels strongly exacerbated 0-Mg(2+)-induced epileptiform activity in slices from pilocarpine-treated animals, while having a significantly smaller effect in control tissue. This suggests that in chronically epileptic tissue, network excitability very critically depends on the remaining SK-channel mediated AHP. Additional real-time RT-PCR and semiquantitative Western blot experiments revealed that both the SK2 channel transcript and protein were significantly downregulated in the epileptic CA1 region. We conclude that SK2 channels are down-regulated in chronic epilepsy underlying the impaired SK channel function in CA1 pyramidal cells, and a further reduction of the remaining critical mass of SK channels results in an acute network decompensation.
authors: Oscar Langendorff Institute of Physiology, University of Rostock, Gertrudenstrasse 9, 18057 Rostock, Germany.
authors: Robert
authors: R
authors: Schulz
authors: Timo
authors: T
authors: Kirschstein
authors: Hannes
authors: H
authors: Brehme
authors: Katrin
authors: K
authors: Porath
authors: Ulrike
authors: U
authors: Mikkat
authors: Rüdiger
authors: R
authors: Köhling
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*
chemical_list: D051640:Small-Conductance Calcium-Activated Potassium Channels; D010862:Pilocarpine