Epileptiform activity of veratridine model in rat brain slices: effects of antiepileptic drugs.
The effects of the antiepileptic drugs valproic acid (VPA), phenytoin (PHT), and ethosuximide (ESM) on evoked and spontaneous seizure-like (epileptiform) activity were studied in the veratridine epileptiform model in rat brain slices, using conventional electrophysiological intracellular recording techniques. The veratridine model is generated by treatment of brain slices with a low concentration (0.3 microM) of the alkaloid veratridine. The drug modifies sodium channel function so that a brief current injection in hippocampal CA1 pyramidal neurons evokes bursts of epileptiform activity. Therapeutic concentrations of VAP (50-200 microM) inhibited both evoked and spontaneous bursting in a voltage-dependent manner without affecting membrane resting potential or input resistance. Similarly, therapeutic concentrations of PHT (4-15 microM) inhibited both evoked and spontaneous bursting in a voltage-dependent fashion with no apparent change in the membrane resting potential. However, PHT increased the membrane input resistance and elevated the firing threshold of neurons. The antiepileptic drug ESM failed to inhibit evoked or spontaneous bursting even at high concentrations. The results suggest that the veratridine model of epileptiform activity is sensitive only to antiepileptic drugs that primarily affect the sodium channels.
Otoom
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SA
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, TX 77204-5515, USA.
Alkadhi
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KA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003292:Convulsants / Q000633:toxicity*; D005013:Ethosuximide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects*; D010672:Phenytoin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology; D014701:Veratridine / Q000633:toxicity*
D000927:Anticonvulsants; D003292:Convulsants; D015222:Sodium Channels; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin; D014701:Veratridine; D012964:Sodium