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Voltage‐dependent gating of NR1/2B NMDA receptors
Author(s) -
Clarke Richard J.,
Johnson Jon W.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.160622
Subject(s) - gating , biophysics , chemistry , depolarization , nmda receptor , receptor , agonist , ion channel , protein subunit , membrane potential , kinetics , voltage clamp , biochemistry , biology , physics , quantum mechanics , gene
Ligand‐gated ion channels are activated by agonist binding, but may also be modulated by membrane voltage. N ‐Methyl‐ d ‐aspartate receptors (NMDARs) exhibit especially strong voltage dependence due to channel block by external Mg 2+ (Mg o 2+ ) . Here we demonstrate that activity of NMDARs composed of NR1 and NR2B subunits (NR1/2B receptors) is enhanced by depolarization even in 0 Mg o 2+ , causing slow current relaxations in response to rapid voltage changes. We present a kinetic model of receptor activation that incorporates voltage‐dependent gating‐associated NR2B subunit conformational changes. The model accurately reproduces current relaxations during depolarizations and subsequent repolarizations in 0 Mg o 2+ . Model simulations in physiological Mg o 2+ concentrations show that voltage‐dependent receptor gating also underlies the slow component of Mg o 2+ unblock, a phenomenon that previously was shown to influence Mg o 2+ unblock kinetics during dendritic spikes. We propose that voltage‐dependent gating of NR1/2B receptors confers enhanced voltage and time dependence on NMDAR‐mediated signalling.