Cortical hyperpolarization-activated depolarizing current takes part in the generation of focal paroxysmal activities.
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.
Timofeev
Igor
I
Laboratory of Neurophysiology, Faculty of Medicine, Laval University, Quebec City, QC, Canada G1K 7P4. Igor.Timofeev@phs.ulaval.ca
Bazhenov
Maxim
M
Sejnowski
Terrence
T
Steriade
Mircea
M
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
D003292:Convulsants; D012964:Sodium; D011188:Potassium; D001640:Bicuculline