Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors

What is it about?

This paper begins to map the sequence of intramolecular interactions that define the opening of the NMDA receptor channel. Here, we identify a direct chemical linkage across receptor subunits that forms during opening and stabilizes open-channel conformations. This interaction is required to maintain the characteristically long current mediated by NMDA receptors, and when absent causes a large deficit in synaptic current, as observed in variants identified in certain patients with neurological disorders.

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Photo by ANIRUDH on Unsplash

Photo by ANIRUDH on Unsplash

Why is it important?

NMDA receptors are glutamate-gated ion channels present on the postsynaptic site of almost all excitatory synapses in brain and spinal cord. They respond to synaptic stimulation with a large calcium-rich current, whose dysregulation is the cause of myriad neuropsychiatric pathologies, including chronic pain, schizophrenia, and neurodegenerative pathologies. If we are to intervene with therapeutics that optimize their function, it is necessary to identify the internal motions and the chemical bonds that control the activation of these veritable nanomachines.