N-methyl-D-aspartate enhancement of the glycine response in the rat sacral dorsal commissural neurons

Tian Le Xu, Xian Ping Dong, Dian Shi Wang

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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 μM 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 μM), blocked the NMDA-induced potentiation of I(Gly), whereas 50 μM CNQX, a non-NMDA receptor antagonist, did not. The potentiation effect was reduced when NMDA was applied in a Ca2+-free extracellular solution or in the presence of BAPTA AM, and was independent of the activation of voltage-dependent Ca2+ channels. Pretreatment with KN-62, a selective Ca2+-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 Ca2+ 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.

Original languageEnglish
Pages (from-to)1647-1653
Number of pages7
JournalEuropean Journal of Neuroscience
Volume12
Issue number5
DOIs
Publication statusPublished - 2000
Externally publishedYes

ASJC Scopus Subject Areas

  • General Neuroscience

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