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J Neurophysiol (January 28, 2004). doi:10.1152/jn.00523.2003
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Submitted on May 30, 2003
Accepted on January 22, 2004

Contribution of intrinsic neuronal factors in the generation of cortically driven electrographic seizures

Igor Timofeev*, Francois Grenier, and Mircea Steriade

* To whom correspondence should be addressed. E-mail: Igor.Timofeev{at}phs.ulaval.ca.

Some electrographic seizures are generated intracortically. The cellular and ionic bases of cortically generated spontaneous seizures are not fully understood. Here, we investigated spontaneously occurring seizures consisting of spike-wave complexes intermingled with fast runs in ketamine-xylazine anesthetized cats, using dual intracellular recordings in which one pipette contained a control solution and another pipette contained blockers of either K+ or Na+ or Ca2+ currents. We show that closely located neocortical neurons display virtually identical fluctuations of the membrane potential during electrographic seizures, thus directly demonstrating a high degree of focal synchrony during paroxysmal activity. In addition to synaptic drives, the persistent Na+ current (INa(p)) and probably the high-threshold Ca2+ current contributed to the generation of paroxysmal depolarizing shifts (PDSs) during cortically driven seizures. Ca2+-activated K+ current (IK(Ca)) took also part in the control of the amplitude and duration of PDSs. The hyperpolarizing components of seizures largely depended on Cs+-sensitive K+ currents. IK(Ca) played a significant, while not exclusive, role in the mediation of hyperpolarizing potentials related to EEG "waves" during spike-wave seizures. We conclude that intrinsic cellular factors have significant role in the generation of depolarizing and hyperpolarizing components of seizures.




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