title: Cortical hyperpolarization-activated depolarizing current takes part in the generation of focal paroxysmal activities.
abstract: During paroxysmal neocortical oscillations, sudden depolarization leading to the next cycle occurs when the majority of cortical neurons are hyperpolarized. Both the Ca(2+)-dependent K(+) currents (I(K(Ca))) and disfacilitation play critical roles in the generation of hyperpolarizing potentials. In vivo experiments and computational models are used here to investigate whether the hyperpolarization-activated depolarizing current (I(h)) in cortical neurons also contributes to the generation of paroxysmal onsets. Hyperpolarizing current pulses revealed a depolarizing sag in approximately 20% of cortical neurons. Intracellular recordings from glial cells indirectly indicated an increase in extracellular potassium concentration ([K(+)](o)) during paroxysmal activities, leading to a positive shift in the reversal potential of K(+)-mediated currents, including I(h). In the paroxysmal neocortex, approximately 20% of neurons show repolarizing potentials originating from hyperpolarizations associated with depth-electroencephalogram positive waves of spike-wave complexes. The onset of these repolarizing potentials corresponds to maximal [K(+)](o) as estimated from dual simultaneous impalements from neurons and glial cells. Computational models showed how, after the increased [K(+)](o), the interplay between I(h), I(K(Ca)), and a persistent Na(+) current, I(Na(P)), could organize paroxysmal oscillations at a frequency of 2-3 Hz.
authors.affiliation: Laboratory of Neurophysiology, Faculty of Medicine, Laval University, Quebec City, QC, Canada G1K 7P4. Igor.Timofeev@phs.ulaval.ca
authors.forename: Igor
authors.initials: I
authors.lastname: Timofeev
authors.forename: Maxim
authors.initials: M
authors.lastname: Bazhenov
authors.forename: Terrence
authors.initials: T
authors.lastname: Sejnowski
authors.forename: Mircea
authors.initials: M
authors.lastname: Steriade
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000633:toxicity; D002415:Cats; D003292:Convulsants / Q000633:toxicity; D004569:Electroencephalography; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D019579:Neocortex / Q000187:drug effects / Q000503:physiopathology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D012964:Sodium / Q000378:metabolism
chemical_list: D003292:Convulsants; D012964:Sodium; D011188:Potassium; D001640:Bicuculline