Distinct gating modes determine the biphasic relaxation of NMDA receptor currents

Abstract

Following brief stimulation, macroscopic NMDA receptor currents decay with biphasic kinetics that is believed to reflect glutamate dissociation and receptor desensitization. We found that the fast and slow decay components arise from the simultaneous deactivation of receptor populations that gate with short and long openings, respectively. Because individual receptors switched infrequently between gating modes, the relaxation time course was largely determined by the proportion of channels in each gating mode at the time of stimulation.

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Figure 1: Deactivation and desensitization of NR1/NR2A channels.
Figure 2: Neuronal NMDA receptors display modal gating.
Figure 3: Modal gating accounts for biphasic decay.

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Acknowledgements

This work was supported in part by grants from the US National Institutes of Health (to J.R.H. and G.K.P.), the American Heart Association (to G.K.P.) and a travel grant from the Department of Anesthesiology (to G.K.P.).

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Correspondence to Gabriela K Popescu.

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Supplementary Figure 1, Supplementary Table 1, Supplementary Methods and Supplementary Results (PDF 251 kb)

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Zhang, W., Howe, J. & Popescu, G. Distinct gating modes determine the biphasic relaxation of NMDA receptor currents. Nat Neurosci 11, 1373–1375 (2008). https://doi.org/10.1038/nn.2214

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