HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 574/2/477    most recent jphysiol.2006.112193v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wyllie, D. J. A. Articles by Chen, P. E. Search for Related Content PubMed PubMed Citation Articles by Wyllie, D. J. A. Articles by Chen, P. E. Related Collections Neuroscience

¹ Centre for Neuroscience Research, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK
² Department of Neuroscience, Brown University, 190 Thayer Street, Providence, RI 02912, USA

We have examined the function of a conserved serine residue (Ser670) in the S2 ligand-binding region of the NR2A N-methyl-D-aspartate (NMDA) receptor subunit, using recombinant NR1/NR2A receptors expressed in Xenopus laevis oocytes. Mutation of Ser670 to glycine (S670G) in NR2A reduced the potency of glutamate by 124-fold. Single-channel conductance and the duration of apparent open periods of NR2A(S670G) receptor mutants were, however, indistinguishable from wild-type NMDA receptors. NR1/NR2A(S670G) shut-time distributions were best described by a mixture of six exponential components, and the four shortest shut intervals of each distribution were considered to occur within a channel activation (burst). Bursts of single-channel openings were fitted with a mixture of four exponential components. The longest two components carried the majority of the charge transfer and had mean durations of 9.6 ± 0.5 and 29.6 ± 1.5 ms. The overall channel open probability during a burst was high (mean, 0.83 ± 0.06). Consistent with a shortening of NMDA receptor-channel burst lengths was the observation of an increased deactivation rate of macroscopic currents evoked by brief applications of glutamate to outside-out membrane patches. Correlations between shut times and adjacent open times were observed in all data records. Noticeably, shorter than average openings tended to occur next to long closed periods, whereas longer than average openings tended to occur next to short closings. Our single-channel data, together with modelling using a kinetic scheme to describe channel activations, support our hypothesis that the S670G point mutation reduces the dwell time of glutamate in its binding site.

(Received 25 April 2006; accepted after revision 12 May 2006; first published online 18 May 2006)
Corresponding author D. J. A. Wyllie: Centre for Neuroscience Research, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK. Email: dwyllie1{at}staffmail.ed.ac.uk

This article has been cited by other articles:

				S. M. Dravid, A. Prakash, and S. F. Traynelis Activation of recombinant NR1/NR2C NMDA receptors J. Physiol., September 15, 2008; 586(18): 4425 - 4439. [Abstract] [Full Text] [PDF]

				K. Erreger and S. F. Traynelis Zinc inhibition of rat NR1/NR2A N-methyl-D-aspartate receptors J. Physiol., February 1, 2008; 586(3): 763 - 778. [Abstract] [Full Text] [PDF]

				D. C. Wrighton, E. J. Baker, P. E. Chen, and D. J. A. Wyllie Mg2+ and memantine block of rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes J. Physiol., January 1, 2008; 586(1): 211 - 225. [Abstract] [Full Text] [PDF]

				P. E. Chen, M. T. Geballe, E. Katz, K. Erreger, M. R. Livesey, K. K. O'Toole, P. Le, C. J. Lee, J. P. Snyder, S. F. Traynelis, et al. Modulation of glycine potency in rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes J. Physiol., January 1, 2008; 586(1): 227 - 245. [Abstract] [Full Text] [PDF]

				K. Erreger, M. T. Geballe, A. Kristensen, P. E. Chen, K. B. Hansen, C. J. Lee, H. Yuan, P. Le, P. N. Lyuboslavsky, N. Micale, et al. Subunit-Specific Agonist Activity at NR2A-, NR2B-, NR2C-, and NR2D-Containing N-Methyl-D-aspartate Glutamate Receptors Mol. Pharmacol., October 1, 2007; 72(4): 907 - 920. [Abstract] [Full Text] [PDF]

				P. A. Frizelle, P. E. Chen, and D. J. A. Wyllie Equilibrium Constants for (R)-[(S)-1-(4-Bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic Acid (NVP-AAM077) Acting at Recombinant NR1/NR2A and NR1/NR2B N-Methyl-D-aspartate Receptors: Implications for Studies of Synaptic Transmission Mol. Pharmacol., September 1, 2006; 70(3): 1022 - 1032. [Abstract] [Full Text] [PDF]

				A. J. Gibb Glutamate unbinding reveals new insights into NMDA receptor activation J. Physiol., July 15, 2006; 574(2): 329 - 329. [Full Text] [PDF]