Zinc release from Schaffer collaterals and its significance.
On the basis of the evidence that approximately 45% of Schaffer collateral boutons are zinc-positive, zinc release from Schaffer collaterals and its action were examined in hippocampal slices. When zinc release from Schaffer collaterals was examined using ZnAF-2, a membrane-impermeable zinc indicator, ZnAF-2 signal in the stratum radiatum of the CA1 was increased by tetanic stimuli at 100 Hz for 1s, suggesting that zinc is released from Schaffer collaterals in a calcium- and impulse-dependent manner. An in vivo microdialysis experiment indicated that the perfusion with 10 microM zinc significantly decreases extracellular glutamate concentration in the CA1. When tetanic stimuli at 100 Hz for 5s were delivered to the dentate granule cells, the increase in calcium signal in the stratum radiatum of the CA1, as well as in the stratum lucidum of the CA3, was attenuated by addition of 10 microM zinc, while enhanced by addition of 1mM CaEDTA, a membrane-impermeable zinc chelator. The increase in calcium signal in the CA1, in which Schaffer collateral synapses exist, during delivery of tetanic stimuli at 100 Hz for 1s to the Schaffer collateral-commissural pathway was also significantly enhanced by addition of 1mM CaEDTA. These results suggest that zinc released from Schaffer collaterals suppressively modulates presynaptic and postsynaptic calcium signaling in the CA1, followed by the suppression of glutamate release.
Takeda
Atsushi
A
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp
Nakajima
Satoko
S
Fuke
Sayuri
S
Sakurada
Naomi
N
Minami
Akira
A
Oku
Naoto
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007202:Indicators and Reagents; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*; D011725:Pyridines; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D015032:Zinc / Q000378:metabolism*
D002614:Chelating Agents; D007202:Indicators and Reagents; D011725:Pyridines; C462061:ZnAF-2; D018698:Glutamic Acid; D015032:Zinc; D002118:Calcium