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The Journal of Neurophysiology Vol. 83 No. 1 January 2000, pp. 616-620
Copyright ©2000 by the American Physiological Society
2 (NR2B) Subunit
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098
Tovar, Kenneth R.,
Kathleen Sprouffske, and
Gary L. Westbrook.
Fast NMDA Receptor-Mediated Synaptic Currents in Neurons From
Mice Lacking the 2 (NR2B) Subunit. J. Neurophysiol. 83: 616-620, 2000. The
N-methyl-D-aspartate (NMDA) receptor has
been implicated in the formation of synaptic connections. To
investigate the role of the 
2 (NR2B) NMDA receptor subunit, which is
prominently expressed during early development, we used neurons from
mice lacking this subunit. Although 2
/ mice die soon
after birth, we examined whether NMDA receptor targeting to the
postsynaptic membrane was dependent on the 2 subunit by rescuing
hippocampal neurons from these mice and studying them in autaptic
cultures. In voltage-clamp recordings, excitatory postsynaptic currents
(EPSCs) from 2/ neurons expressed an NMDA
receptor-mediated EPSC that was apparent as soon as synaptic activity
developed. However, compared with wild-type neurons, NMDA
receptor-mediated EPSC deactivation kinetics were much faster and were
less sensitive to glycine, but were blocked by Mg2+ or AP5.
Whole cell currents from 2/ neurons were also more
sensitive to block by low concentrations of Zn2+ and much
less sensitive to the 2-specific antagonist ifenprodil than
wild-type currents. The rapid NMDA receptor-mediated EPSC deactivation
kinetics and the pharmacological profile from 2/
neurons are consistent with the expression of 
1/1 diheteromeric receptors in excitatory hippocampal neurons from mice lacking the 2
subunit. Thus 1 can substitute for the 2 subunit at synapses and
2 is not required for targeting of NMDA receptors to the postsynaptic membrane.
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