title: Inhibition modifies the effects of slow calcium-activated potassium channels on epileptiform activity in a neuronal network model.
abstract: Generation of epileptiform activity typically results from a change in the balance between network excitation and inhibition. Experimental evidence indicates that alterations of either synaptic activity or intrinsic membrane properties can produce increased network excitation. The slow Ca(2+)-activated K(+) currents (sI(AHP)) are important modulators of neuronal firing rate and excitability and have important established and potential roles in epileptogenesis. While the effects of changes in sI(AHP) on individual neuronal excitability are readily studied and well established, the effects of such changes on network behavior are less well known. The experiments here utilize a defined small network model of multicompartment pyramidal cells and an inhibitory interneuron to study the effects of changes in sI(AHP) on network behavior. The benefits of this model system include the ability to observe activity in all cells in a network and the effects of interactions of multiple simultaneous influences. In the model with no inhibitory interneuron, increasing sI(AHP) results in progressively decreasing burst activity. Adding an inhibitory interneuron changes the observed effects; at modest inhibitory strengths, increasing sI(AHP) in all network neurons actually results in increased network bursting (except at very high values). The duration of the burst activity is influenced by the length of delay in a feedback loop, with longer loops resulting in more prolonged bursting. These observations illustrate that the study of potential antiepileptogenic membrane effects must be extended to realistic networks. Network inhibition can dramatically alter the observations seen in pure excitatory networks.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. khyang@jhmi.edu.
authors.forename: K-H
authors.initials: KH
authors.lastname: Yang
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Franaszczuk
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Bergey
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D005246:Feedback; D008959:Models, Neurological; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D016571:Neural Networks, Computer; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D024681:Potassium Channels, Calcium-Activated; D005680:gamma-Aminobutyric Acid