title: Contrasting effects of the persistent Na+ current on neuronal excitability and spike timing.
abstract: The persistent Na+ current, INaP, is known to amplify subthreshold oscillations and synaptic potentials, but its impact on action potential generation remains enigmatic. Using computational modeling, whole-cell recording, and dynamic clamp of CA1 hippocampal pyramidal cells in brain slices, we examined how INaP changes the transduction of excitatory current into action potentials. Model simulations predicted that INaP increases afterhyperpolarizations, and, although it increases excitability by reducing rheobase, INaP also reduces the gain in discharge frequency in response to depolarizing current (f/I gain). These predictions were experimentally confirmed by using dynamic clamp, thus circumventing the longstanding problem that INaP cannot be selectively blocked. Furthermore, we found that INaP increased firing regularity in response to sustained depolarization, although it decreased spike time precision in response to single evoked EPSPs. Finally, model simulations demonstrated that I(NaP) increased the relative refractory period and decreased interspike-interval variability under conditions resembling an active network in vivo.
authors.affiliation: Department of Physiology, Institute of Basal Medicine, University of Oslo, PB 1103 Blindern, N-0317 Oslo, Norway.
authors.forename: Koen
authors.initials: K
authors.lastname: Vervaeke
authors.forename: Hua
authors.initials: H
authors.lastname: Hu
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Graham
authors.forename: Johan F
authors.initials: JF
authors.lastname: Storm
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015222:Sodium Channels; D013779:Tetrodotoxin