Veratridine-treated brain slices: a cellular model for epileptiform activity.
This study introduces veratridine-treated brain slices as a new in vitro synaptic-independent model for epileptiform discharge. Studies were performed on the hippocampus in rat brain slices using conventional electrophysiological intracellular recording techniques. Veratridine (0.3 microM) produced a time-dependent blockade of synaptic transmission as indicated by inhibition of the evoked population spike in the region CA1 of the hippocampus. However, in the same slices, intracellularly-evoked single action potentials were converted to epileptiform bursting shortly after exposure to veratridine. Additionally, in the veratridine model, spontaneous epileptiform activity developed after prolonged (more than 45 min) superfusion. The model was utilized to examine the action of two antiepileptic drugs: a sodium channel dependent and a synaptic dependent antiepileptic agents. Therapeutic concentrations of valproic acid (VPA, 10-100 microM) inhibited both evoked and spontaneous bursting induced by veratridine. However, therapeutic concentrations of the synaptic-dependent antiepileptic drug phenobarbital (20-40 microM) failed to inhibit veratridine-induced bursting. These results demonstrate that the veratridine-treated brain slice is a simple and reliable model for studying mechanisms of action and for screening of potential sodium channel-dependent antiepileptic drugs.
Otoom
S
S
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, TX 77204-5515, USA.
Tian
L M
LM
Alkadhi
K A
KA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*
D000927:Anticonvulsants; D014635:Valproic Acid; D014701:Veratridine; D010634:Phenobarbital