Bicuculline increases Ca2+ transients in rat cerebellar granule cells through non-GABA(A) receptor associated mechanisms.
The effects of bicuculline methiodide (bicuculline) and gabazine, two GABA(A) antagonists, on cytosolic calcium increases (Ca2+ transients) in rat cerebellar granule cells were examined using Fluo-3-spectrofluorometry. Bicuculline (25 microM) markedly potentiated Ca2+ transients caused by KCl (25 mM) and by A23187 (4 microM) whereas gabazine (25 microM) had no effect. Calcium increases caused by glutamate (2 microM), N-methyl-D-aspartic acid (200 microM), trans-1-amino-cyclopentane-1,3 dicarboxylate (200 microM), thapsigargin (1 microM) or caffeine (5 mM) were not altered by bicuculline. Thapsigargin, which depletes intracellular Ca2+ stores, had no effect on either KCl- or A23187-induced Ca2+ transients, but completely blocked bicuculline-induced potentiation of Ca2+ increases. Our data suggest that bicuculline triggers calcium release when calcium entry is evoked by KCl or A23187 and that this effect is not mediated via GABA(A) receptor blockade.
D000814:Aniline Compounds; D000818:Animals; D001640:Bicuculline / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D018756:GABA Antagonists / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D013050:Spectrometry, Fluorescence; D019284:Thapsigargin / Q000494:pharmacology; D014966:Xanthenes