A glycine receptor antagonist, strychnine, blocked NMDA receptor activation in the neonatal mouse neocortex.
The NMDA receptor (NMDAR) is a Ca (2+)-permeable cation channel that plays a critical role in neural network formation during brain development. Since it is blocked in a voltage-dependent manner by extracellular Mg(2+), in order for the NMDA to be activated, the membrane must be strongly depolarized. Immature neurons in the developing neocortex can be depolarized by ligand-gated Cl(-) channels, such as the glycine receptor (GlyR) or GABA(A) receptor (GABA(A) R). We here assess the contribution of GlyRs to Ca(2+) influx via NMDARs in neonatal mouse cortical neurons. The GlyR antagonist, strychnine, was more effective in suppressing postsynaptic Ca(2+) influx than the GABA(A) R antagonist, picrotoxin, suggesting greater potentiation of NMDARs by GlyRs than by GABA(A) Rs. The GlyR, known to be endogenously activated at this stage, may play a critical role in neocortical development.
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002118:Calcium; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents; D007736:Kynurenic Acid; D008274:Magnesium; D016202:N-Methylaspartate; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D013331:Strychnine; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; C084485:7-chlorothiokynurenic acid