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Updated: Dec 4, 2025
04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
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Allosteric Changes in the NMDA Receptor Associated with Calcium-Dependent Inactivation
Nidhi Kaur Bhatia1, Elisa Carrillo1, Ryan J Durham2
1Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, Texas.
Biophysical Journal
|October 25, 2020
Summary
Calcium-calmodulin binding to N-methyl-D-aspartate (NMDA) receptors influences their structure and function. This interaction affects receptor gating and may explain calcium-dependent inactivation of synaptic signaling.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- N-methyl-D-aspartate (NMDA) receptors are crucial for excitatory synaptic transmission in the central nervous system.
- Calcium influx via NMDA receptors triggers channel inactivation, a process involving calmodulin.
- Calmodulin binds to the intracellular C-terminal segment of the GluN1 subunit, regulating receptor activity.
Purpose of the Study:
- To investigate the structural and functional effects of calcium-calmodulin binding on NMDA receptors.
- To elucidate the allosteric mechanisms underlying NMDA receptor inactivation.
Main Methods:
- Single-molecule Förster Resonance Energy Transfer (FRET) investigations.
- Biophysical analysis of NMDA receptor conformational changes.
Main Results:
- Calcium-calmodulin binding shortens the distance between GluN1 subunits at the transmembrane segment entrance.
- Glycine-binding domain cleft closure is enhanced by calcium-calmodulin.
- Glycine deactivation rate is reduced in the presence of calcium-calmodulin.
Conclusions:
- Calcium-calmodulin binding induces long-range allosteric effects on extracellular receptor segments.
- These allosteric changes likely contribute to the calcium-dependent inactivation of NMDA receptors.
- Understanding these mechanisms is vital for comprehending synaptic plasticity and neurological disorders.
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