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

• Published in: Journal of neurophysiology 2005-01, Vol.93 (1), p.178
• Main Authors: Maher, Brady J, MacKinnon, Roger L., II, Bai, Jihong, Chapman, Edwin R, Kelly, Paul T
• Format: Article
• Language: English
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00651.2004

1 Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas; and 2 Department of Physiology, The University of Wisconsin, Madison, Wisconsin Submitted 28 June 2004; accepted in final form 15 August 2004 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. Address for reprint requests and other correspondence: P. T. Kelly, Dept. of Molecular Biosciences, 4006 Haworth Hall, The University of Kansas, Lawrence, KS 66045-2106 (E-mail: ptkelly{at}ku.edu )