![]() This may partially explain the wide range of physiological outcomes associated with NMDAR signaling. The influence of NMDAR subunit composition on Ca signaling suggests that activation of receptors composed of distinct subunit combinations may trigger different biological pathways. For similar reasons, receptors containing different NR2 subunits generate Ca transients with different time courses. NR2C- and NR2D-containing receptors generate the smallest and longest lasting currents. In comparison, current influx through NR2B-containing receptors is also large but lasts far longer. For these reasons, activation of NR2A-containing receptors generates relatively large and fast currents. Finally, single-channel conductance is subunit-dependent such that NR2A- and NR2B-containing receptors conduct nearly twice as much current as NR2C- and NR2D-containing receptors. Similarly, receptor affinity for Magnesium (Mg) also varies with the NR2 subunit such that NR2A and NR2B are more susceptible to block by extracellular Mg and show greater voltage dependence than NR2C and NR2D. Receptors containing the NR2A subunit generate currents that decay rapidly (t ~120 msec) in comparison to those containing NR2B and NR2C (t ~400 msec) or NR2D (t ~5 sec). Thus, differential glutamate affinity may explain some of the variability in NMDAR deactivation kinetics. Generally, high binding affinity indicates a low dissociation rate of glutamate from the receptor and more prolonged NMDAR opening following glutamate binding. However, the affinity for glutamate differs among the isoforms such that NR2A has the lowest affinity, NR2D the highest, and NR2B and NR2C have intermediate affinities. This structural diversity is functionally relevant the specific subunit composition of a receptor along with the timing and magnitude of local membrane potential fluctuations determines the duration and magnitude of Ca current through NMDARs.Įach of the four NR2 subunits (NR2A through D) has a glutamate binding site. Each subunit has multiple isoforms and in some cases multiple splice variants. NMDARs are heteromeric tetramers typically composed of NR1 subunits and NR2 or NR3 subunits. SUBUNIT DEPENDENCE Of NMDA RECEPTOR-MEDIATED CALCIUM INFLUX ![]()
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