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. 2016 Nov 18;6:36684. doi: 10.1038/srep36684

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Copyright © 2016, The Author(s)

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Muscarine stimulation of M1Rs can potentiate GluN2AR containing NMDARs (GluN2ARs) via a sequential cascade leading to the recruitment of Src and increased tyrosine phosphorylation of GluN2A subunits. Potentiation of GluN2AR by Src is facilitated by Ca²⁺ entry via NMDARs. Muscarine can depress GluN2ARs via IP₃R-dependent recruitment of STEP leading to decreased tyrosine phosphorylation of GluN2A subunits. The balance between Src and STEP activation can be altered by varying the intracellular concentration of EGTA ([EGTA]_i); increased [EGTA]_I favors Src- over STEP-mediated regulation of GluN2ARs.