CALCIUM-DEPENDENT DESENSITIZATION OF NMDA RECEPTORS
Glutamate receptors play the key role in excitatory synaptic transmission in central nervous system (CNS). N-methyl-D-aspartate-activated glutamate receptor subtype (NMDAR) is permeable to sodium and calcium and is expressed in pre- and post-synapse as well as in extrasynaptic area of neuronal membrane. Calcium entry into dendritic spines is critically important for long-term potentiation and long-term depression of synaptic transmission. These events are thought to represent morpho-functional changes of memory formation. NMDARs dysfunction is involved in epilepsy, schizophrenia, migraine, dementia and other neurodegenerative diseases. Prolonged activation of extrasynaptic NMDARs causes neuronal calcium overload and apoptosis. Here we review the contemporary findings concerning the molecular mechanisms of NMDARs calcium-dependent desensitization, which allows fast modulation of these receptors in CNS and limits calcium entry into cell in pathological conditions. Here we present the data on molecular NMDAR determinants related to calcium-dependent desensitization as well as new data on local functional interaction of NMDARs with other ion channels and transporters. We also describe association of NMDARs with membrane lipid microdomains.