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Received November 24, 2004
Revised December 15, 2004
Accepted after revision January 7, 2005
1 Emory University
2 NIH
3 University of Edinburgh
* To whom correspondence should be addressed. E-mail: drkeverreger{at}netscape.net.
NR2A and NR2B are the predominant NR2 NMDA receptor subunits expressed in cortex and hippocampus. The relative expression level of NR2A and NR2B is regulated developmentally and these two subunits have been suggested to play distinct roles in long-term synaptic plasticity. We have used patch-clamp recording of recombinant NMDA receptors expressed in HEK 293 cells to characterize the activation properties of both NR1/NR2A and NR1/NR2B receptors. Recordings from outside-out patches that contain a single active channel show that NR2A-containing receptors have a higher probability of opening at least once in response to a brief synaptic-like pulse of glutamate than NR2B-containing receptors (NR2A 0.80, NR2B 0.56), a higher peak open probability (NR2A 0.50, NR2B 0.12), and a higher open probability within an activation (NR2A 0.67, NR2B 0.37). Analysis of the sequence of single-channel open and closed intervals shows that both NR2A and NR2B containing receptors undergo multiple conformational changes prior to opening of the channel, with at least one of these steps being faster for NR2A than NR2B. These distinct properties produce profoundly different temporal signaling profiles for NR2A and NR2B containing receptors. Simulations of synaptic responses demonstrate that at low frequencies typically used to induce LTD (
1 Hz), NR1/NR2B makes a larger contribution to total charge transfer and therefore calcium influx than NR1/NR2A. However, under high frequency tetanic stimulation (100 Hz; >100ms) typically used to induce LTP, the charge transfer mediated by NR1/NR2A considerably exceeds that of NR1/NR2B.
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