Thapsigargin inhibits bicuculline-induced epileptiform excitability in rat hippocampal slices.
Evoked field potentials were recorded in the CA3 region of rat hippocampal slices to detect whether intracellular Ca2+ stores are involved in the epileptiform effects of the two prototypic GABA(A) antagonists, bicuculline methiodide (BMI) and gabazine (SR-95531; GBZ). Field population spikes gradually increased and became repetitive (epileptiform bursting) in the presence of either BMI (5 microM), or GBZ (5 microM). Thapsigargin (2 microM), a depletor of intracellular Ca2+ stores, reduced the epileptiform effect of BMI, but had no significant effect on the GBZ-induced hyperexcitability. These data suggest that Ca2+ release from intracellular stores participates in the epileptiform response of hippocampal CA3 neurons to BMI, but not in the response to GBZ.
Wülfert
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UCB s.a. Pharma Sector, Research and Development, Braine-l'Alleud, Belgium.
Margineanu
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DG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009924:Organ Culture Techniques; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology*
D003292:Convulsants; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D011724:Pyridazines; D019284:Thapsigargin; C049853:gabazine; D002118:Calcium; D001640:Bicuculline