title: Activation of postsynaptic Ca(2+) stores modulates glutamate receptor cycling in hippocampal neurons.
abstract: We show that activation of postsynaptic inositol 1,4,5-tris-phosphate receptors (IP(3)Rs) with the IP(3)R agonist adenophostin A (AdA) produces large increases in AMPA receptor (AMPAR) excitatory postsynaptic current (EPSC) amplitudes at hippocampal CA1 synapses. Co-perfusion of the Ca(2+) 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 IP(3)R-mediated Ca(2+) release can enhance AMPAR EPSC amplitudes through mechanisms that involve AMPAR-PDZ interactions and/or synaptotagmin-SNARE-mediated receptor trafficking.
authors.affiliation: Department of Molecular Biosciences, 4006 Haworth Hall, The University of Kansas, Lawrence, KS 66045-2106, USA.
authors.forename: Brady J
authors.initials: BJ
authors.lastname: Maher
authors.forename: Roger L
authors.initials: RL
authors.lastname: Mackinnon
authors.forename: Jihong
authors.initials: J
authors.lastname: Bai
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chapman
authors.forename: Paul T
authors.initials: PT
authors.lastname: Kelly
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003175:Complement C2 / Q000494:pharmacology; D050678:Complement C2a; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D050600:SNARE Proteins; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050857:Synaptotagmins; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002614:Chelating Agents; D003175:Complement C2; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C033652:postsynaptic density proteins; D050857:Synaptotagmins; C085029:adenophostin A; D004533:Egtazic Acid; D050678:Complement C2a; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000241:Adenosine; D002118:Calcium