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N‐methyl‐ d ‐aspartate enhancement of the glycine response in the rat sacral dorsal commissural neurons
Author(s) -
Le Xu Tian.,
Dong XianPing,
Wang DianShi
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00065.x
Subject(s) - nmda receptor , long term potentiation , cnqx , chemistry , gabaa receptor , bapta , glycine receptor , neuroscience , patch clamp , ampa receptor , receptor , pharmacology , biology , glycine , biochemistry , amino acid
The effect of N‐methyl‐ d ‐aspartate (NMDA) on the glycine (Gly) response was examined in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin‐perforated patch‐recording configuration under voltage‐clamp conditions. The application of 100 μ m NMDA to SDCN neurons reversibly potentiated Gly‐activated Cl – currents (I Gly ) without affecting the Gly binding affinity and the reversal potential of I Gly . A selective NMDA receptor antagonist, APV (100 μ m ), blocked the NMDA‐induced potentiation of I Gly , whereas 50 μ m CNQX, a non‐NMDA receptor antagonist, did not. The potentiation effect was reduced when NMDA was applied in a Ca 2+ ‐free extracellular solution or in the presence of BAPTA AM, and was independent of the activation of voltage‐dependent Ca 2+ channels. Pretreatment with KN‐62, a selective Ca 2+ –calmodulin‐dependent protein kinase II (CaMKII) inhibitor, abolished the NMDA action. Inhibition of calcineurin (CaN) further enhanced the NMDA‐induced potentiation of I Gly . In addition, the GABA A receptor‐mediated currents were suppressed by NMDA receptor activation in the SDCN neurons. The present results show that Ca 2+ entry through NMDA receptors modulates the Gly receptor function via coactivation of CaMKII and CaN in the rat SDCN neurons. This interaction may represent one of the important regulatory mechanisms of spinal nociception. The results also suggest that GABA A and Gly receptors may be subject to different intracellular modulatory pathways.