Back to Search Start Over

Activation of Postsynaptic Ca2+Stores Modulates Glutamate Receptor Cycling in Hippocampal Neurons

Authors :
Roger L. MacKinnon
Jihong Bai
Paul T. Kelly
Brady J. Maher
Edwin R. Chapman
Source :
Journal of Neurophysiology. 93:178-188
Publication Year :
2005
Publisher :
American Physiological Society, 2005.

Abstract

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 Ca2+release can enhance AMPAR EPSC amplitudes through mechanisms that involve AMPAR-PDZ interactions and/or synaptotagmin-SNARE-mediated receptor trafficking.

Details

ISSN :
15221598 and 00223077
Volume :
93
Database :
OpenAIRE
Journal :
Journal of Neurophysiology
Accession number :
edsair.doi.dedup.....85685641ce04c55d8daba263d2e70f36
Full Text :
https://doi.org/10.1152/jn.00651.2004