Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit

Michael D. Ehlers, Su Zhang, Jeffrey P. Bernhardt, Richard L. Huganir

Research output: Contribution to journalArticlepeer-review

451 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)745-755
Number of pages11
Issue number5
StatePublished - Mar 8 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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