Abstract
NMDA (N-methyl-D-aspartate) receptors are excitatory neurotransmitter receptors in the brain critical for synaptic plasticity and neuronal development. These receptors are Ca2+-permeable glutamate-gated ion channels whose physiological properties are regulated by intracellular Ca2+. We report here the purification of a 20 kDa protein identified as calmodulin that interacts with the NR1 subunit of the NMDA receptor. Calmodulin binding to the NR1 subunit is Ca2+ dependent and occurs with homomeric NR1 complexes, heteromeric NR1/NR2 subunit complexes, and NMDA receptors from brain. Furthermore, calmodulin binding to NR1 causes a 4-fold reduction in NMDA channel open probability. These results demonstrate that NMDA receptor function can be regulated by direct binding of calmodulin to the NR1 subunit, and suggest a possible mechanism for activity-dependent feedback inhibition and Ca2+-dependent inactivation of NMDA receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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Calcium / pharmacology
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Calmodulin / metabolism*
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Calmodulin / pharmacology*
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Cell Line
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Cerebral Cortex / metabolism*
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Egtazic Acid
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Humans
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Ion Channels / drug effects
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Ion Channels / physiology
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Kinetics
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Macromolecular Substances
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Molecular Sequence Data
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Mutagenesis, Insertional
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Mutagenesis, Site-Directed
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Oligodeoxyribonucleotides
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Peptide Fragments / chemistry
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Peptide Fragments / isolation & purification
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / chemistry
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Transfection
Substances
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Calmodulin
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Ion Channels
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Macromolecular Substances
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Oligodeoxyribonucleotides
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Peptide Fragments
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Receptors, N-Methyl-D-Aspartate
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Recombinant Proteins
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Egtazic Acid
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Calcium