title: Facilitation of zinc influx via AMPA/kainate receptor activation in the hippocampus.
abstract: Glutamate and zinc is co-released by excitation of hippocampal mossy fibers and both concentrations are increased in the extracellular compartment. In a novel environment, however, extracellular zinc is persistently decreased in spite of the increase in extracellular glutamate. The mechanism of the decrease in extracellular zinc was studied in the present paper. In rats subjected to the novelty stress under hippocampal perfusion, the differential changes in extracellular glutamate and zinc were abolished in the presence of 1 microM tetrodotoxin (TTX), a sodium channel blocker, which reduced exploratory behavior. When the hippocampus was perfused with corticosterone (50 ng/ml), extracellular zinc was increased. These results suggest that glutamatergic neuron activation elicited by novelty stress is involved in the decrease in extracellular zinc and that glucocorticoid is not a trigger for its decrease. The differential changes in extracellular glutamate and zinc was induced by electrical stimulation to analyze the decrease in extracellular zinc; the differential changes were elicited by delivery of tetanic stimuli (100 Hz for 1s, 5 min intervals, three times) to the hippocampus instead of the novelty stress, as reported previously. The changes elicited by tetanic stimulation were abolished in the presence of 10 microM CNQX, an AMPA/kainate receptor antagonist. In a hippocampal slice double-labeled with zinc and calcium indicators, furthermore, CNQX inhibited the increase in intracellular zinc levels in mossy fiber synapses after delivery of tetanic stimuli (100 Hz for 5s) to dentate granule cells. The in vivo and in vitro experiments suggest that AMPA/kainate receptor activation is involved in zinc influx into hippocampal cells, followed by the decrease in extracellular zinc. It is likely that zinc influx is persistently facilitated via stress-induced glutamatergic neuron activation.
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE-21, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakurada
authors.forename: Masaki
authors.initials: M
authors.lastname: Ando
authors.forename: Shingo
authors.initials: S
authors.lastname: Kanno
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000494:pharmacology / Q000627:therapeutic use; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D015032:Zinc; D003345:Corticosterone