title: Postsynaptic IP3 receptor-mediated Ca2+ release modulates synaptic transmission in hippocampal neurons.
abstract: Ca(2+)-dependent mechanisms are important in regulating synaptic transmission. The results herein indicate that whole-cell perfusion of inositol 1,4,5-trisphosphate receptor (IP(3)R) agonists greatly enhanced excitatory postsynaptic current (EPSC) amplitudes in postsynaptic hippocampal CA1 neurons. IP(3)R agonist-mediated increases in synaptic transmission changed during development and paralleled age-dependent increases in hippocampal type-1 IP(3)Rs. IP(3)R agonist-mediated increases in EPSC amplitudes were inhibited by postsynaptic perfusion of inhibitors of Ca(2+)/calmodulin, PKC and Ca(2+)/calmodulin-dependent protein kinase II. Postsynaptic perfusion of inhibitors of smooth endoplasmic reticulum (SER) Ca(2+)-ATPases, which deplete intracellular Ca(2+) stores, also enhanced EPSC amplitudes. Postsynaptic perfusion of the IP(3)R agonist adenophostin (AdA) during subthreshold stimulation appeared to convert silent to active synapses; synaptic transmission at these active synapses was completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Postsynaptic IP(3)R-mediated Ca(2+) release also produced a significant increase in spontaneous EPSC frequency. These results indicate that Ca(2+) release from intracellular stores play a key role in regulating the function of postsynaptic AMPARs.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045-2106, USA. ptkelly@ku.edu
authors.forename: Paul T
authors.initials: PT
authors.lastname: Kelly
authors.forename: Roger L
authors.initials: RL
authors.lastname: Mackinnon
authors.forename: Roger V
authors.initials: RV
authors.lastname: Dietz
authors.forename: Brady J
authors.initials: BJ
authors.lastname: Maher
authors.forename: J
authors.initials: J
authors.lastname: Wang
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000241:Adenosine; D001640:Bicuculline; D002118:Calcium; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007211:Indoles; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010852:Picrotoxin; D018160:Receptors, Cytoplasmic and Nuclear; D019284:Thapsigargin; C084782:3-deoxy-3-fluoroinositol 1,4,5-trisphosphate; C085029:adenophostin A; C000543:cyclopiazonic acid