GABAA receptor stimulation enhances NMDA-induced Ca2+ influx in mouse cerebral cortical neurons in primary culture.
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.
Ohkuma
S
S
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Chen
D Z
DZ
Katsura
M
M
Chen
S H
SH
Kuriyama
K
K
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D018118:Chloride Channels / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology*; D007539:Isonicotinic Acids / Q000494:pharmacology; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D001640:Bicuculline; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018118:Chloride Channels; D016291:Dizocilpine Maleate; D018755:GABA Agonists; D007539:Isonicotinic Acids; D009118:Muscimol; D016202:N-Methylaspartate; D010852:Picrotoxin; D011188:Potassium; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C037476:tert-butylbicyclophosphorothionate; C015300:isoguvacine