N-methyl-d-aspartate (NMDA) receptors (NMDARs) are highly expressed in the CNS and mediate the slow component of excitatory transmission. The present study was aimed at characterizing the temperature dependence of the kinetic properties of native NMDARs, with special emphasis on the deactivation of synaptic NMDARs. We used patch-clamp recordings to study synaptic NMDARs at layer II/III pyramidal neurons of the rat cortex, recombinant GluN1/GluN2B receptors expressed in human embryonic kidney (HEK293) cells, and NMDARs in cultured hippocampal neurons. We found that time constants characterizing the deactivation of NMDAR-mediated excitatory postsynaptic currents (EPSCs) were similar to those of the deactivation of responses to a brief application of glutamate recorded under conditions of low NMDAR desensitization (whole-cell recording from cultured hippocampal neurons). In contrast, the deactivation of NMDAR-mediated responses exhibiting a high degree of desensitization (outside-out recording) was substantially faster than that of synaptic NMDA receptors. The time constants characterizing the deactivation of synaptic NMDARs and native NMDARs activated by exogenous glutamate application were only weakly temperature sensitive (Q(10)=1.7-2.2), in contrast to those of recombinant GluN1/GluN2B receptors, which are highly temperature sensitive (Q(10)=2.7-3.7). Ifenprodil reduced the amplitude of NMDAR-mediated EPSCs by approximately 50% but had no effect on the time course of deactivation. Analysis of GluN1/GluN2B responses indicated that the double exponential time course of deactivation reflects mainly agonist dissociation and receptor desensitization. We conclude that the temperature dependences of native and recombinant NMDAR are different; in addition, we contribute to a better understanding of the molecular mechanism that controls the time course of NMDAR-mediated EPSCs.

• MeSH
• Excitatory Amino Acid Antagonists pharmacology   MeSH
• Cell Line MeSH
• Excitatory Postsynaptic Potentials drug effects   physiology   MeSH
• Hippocampus drug effects   physiology   MeSH
• Kinetics MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Glutamic Acid metabolism   MeSH
• Humans MeSH
• Cerebral Cortex drug effects   physiology   MeSH
• Synaptic Transmission drug effects   physiology   MeSH
• Piperidines pharmacology   MeSH
• Rats, Wistar MeSH
• Pyramidal Cells drug effects   physiology   MeSH
• Receptors, N-Methyl-D-Aspartate metabolism   MeSH
• Synapses drug effects   physiology   MeSH
• In Vitro Techniques MeSH
• Temperature * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Excitatory Amino Acid Antagonists MeSH
• ifenprodil MeSH Browser
• Glutamic Acid MeSH
• Piperidines MeSH
• Receptors, N-Methyl-D-Aspartate MeSH