Activation of postsynaptic Ca2+ stores modulates glutamate receptor cycling in hippocampal neurons

Brady J. Maher, Roger L. MacKinnon, Jihong Bai, Edwin R. Chapman, Paul T. Kelly

Research output: Contribution to journalArticlepeer-review


We show that activation of postsynaptic inositol 1,4,5-tris-phosphate receptors (IP3Rs) with the IP3R agonist adenophostin A (AdA) produces large increases in AMPA receptor (AMPAR) excitatory postsynaptic current (EPSC) amplitudes at hippocampal CA1 synapses. Co-perfusion of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N′,N′-tetraacetic acid strongly inhibited AdA-enhanced increases in EPSC amplitudes. We examined the role of AMPAR insertion/anchoring in basal synaptic transmission. Perfusion of an inhibitor of synaptotagmin-soluble n-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor SNARE-mediated exocytosis depressed basal EPSC amplitudes, whereas a peptide that inhibits GluR2/3 interactions with postsynaptic density-95 (PDZ) domain proteins glutamate receptor interacting protein (GRIP)/protein interacting with C-kinase-1 (PICK1) enhanced basal synaptic transmission. These results suggest that constitutive trafficking and anchoring of AMPARs help maintain basal synaptic transmission. The regulation of postsynaptic AMPAR trafficking involves synaptotagmin-SNARE-mediated vesicle exocytosis and interactions between AMPARs and the PDZ domains in GRIP/ PICK1. We show that inhibitors of synaptotagmin-SNARE-mediated exocytosis, or interactions between AMPARs and GRIP/PICK1, attenuated AdA-enhanced increases in EPSC amplitudes. These results suggest that IP3R-mediated Ca 2+ release can enhance AMPAR EPSC amplitudes through mechanisms that involve AMPAR-PDZ interactions and/or synaptotagmin-SNARE-mediated receptor trafficking.

Original languageEnglish (US)
Pages (from-to)178-188
Number of pages11
JournalJournal of neurophysiology
Issue number1
StatePublished - Jan 2005
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


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