dizocilpine-maleate and isoguvacine

The effect of GABAA receptor stimulation on N-methyl-D-aspartate(NMDA)-induced [45Ca2+]influx has been examined using primary cultured cerebral cortical neurons. NMDA induced a dose-dependent increase in [45Ca2+]influx, which was blocked by MK-801 in a dose-dependent manner. GABAA receptor agonists significantly enhanced the NMDA-induced [45Ca2+]influx, and this enhancement was dose-dependently inhibited by bicuculline, although picrotoxin and tert-butyl-bicyclo[2.2.2]phosphoro-thionate (TBPS) exhibited no alterations in this stimulatory action of GABAA receptor agonists. Blockers of L-type voltage-dependent calcium channels significantly reduced the NMDA-induced [45Ca2+]influx. The increased [45Ca2+]influx by both NMDA and GABAA receptor agonists was also reduced by verapamil and nifedipine. These results suggest that the enhancement of NMDA-induced [45Ca2+]influx by GABAA receptor stimulation in immature cerebral cortical neurons may be due to the increased opening of voltage-dependent calcium channel by synergestic actions between NMDA and GABAA receptors.

Topics: Animals; Bicuculline; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Calcium; Calcium Channel Blockers; Calcium Channels; Cells, Cultured; Cerebral Cortex; Chloride Channels; Dizocilpine Maleate; Dose-Response Relationship, Drug; GABA Agonists; Isonicotinic Acids; Mice; Muscimol; N-Methylaspartate; Neurons; Picrotoxin; Potassium; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate