Separate intramolecular targets for protein kinase A control N-Methyl-D-aspartate receptor gating and Ca²⁺ permeability

Background: PKA increases NMDA receptor responses and phosphorylates multiple residues on C-terminal domains (CTD). Results: PKA inhibition reduced gating through GluN2B CTD and reduced Ca²⁺ permeability through GluN1 CTD. Conclusion: PKA controls NMDA receptor gating and Ca²⁺ permeability through distinct sites. Significance: Dissecting the complex modulatory effects of PKA on NMDAreceptors helps delineate fundamental mechanisms of synaptic regulation.