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Calcium-Dependent Desensitization of NMDA Receptors

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Abstract

Glutamate receptors play the key role in excitatory synaptic transmission in the central nervous system (CNS). N-methyl-D-aspartate-activated glutamate receptors (NMDARs) are ion channels permeable to sodium, potassium, and calcium ions that localize to the pre- and postsynaptic membranes, as well as extrasynaptic neuronal membrane. Calcium entry into dendritic spines is essential for long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission. Both LTP and LTD represent morphological and functional changes occurring in the process of memory formation. NMDAR dysfunction is associated with epilepsy, schizophrenia, migraine, dementia, and neurodegenerative diseases. Prolonged activation of extrasynaptic NMDARs causes calcium overload and apoptosis of neurons. Here, we review recent findings on the molecular mechanisms of calcium-dependent NMDAR desensitization that ensures fast modulation of NMDAR conductance in the CNS and limits calcium entry into the cells under pathological conditions. We present the data on molecular determinants related to calcium-dependent NMDAR desensitization and functional interaction of NMDARs with other ion channels and transporters. We also describe association of NMDARs with lipid membrane microdomains.

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Abbreviations

AMPAR:

α-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid receptor

CaM:

calmodulin

NCX:

sodium-calcium exchanger

LTD:

long-term depression

LTP:

long-term potentiation

NMDAR:

N-methyl-D-aspartate receptor

PMCA:

plasma membrane calcium pump

VGCC:

voltage-gated calcium channel

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  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    D. A. Sibarov & S. M. Antonov

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  1. D. A. Sibarov
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Original Russian Text © D. A. Sibarov, S. M. Antonov, 2018, published in Biokhimiya, 2018, Vol. 83, No. 10, pp. 1464–1475.

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Sibarov, D.A., Antonov, S.M. Calcium-Dependent Desensitization of NMDA Receptors. Biochemistry Moscow 83, 1173–1183 (2018). https://doi.org/10.1134/S0006297918100036

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