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.