title: Raised Intracellular Calcium Contributes to Ischemia-Induced Depression of Evoked Synaptic Transmission.
abstract: Oxygen-glucose deprivation (OGD) leads to depression of evoked synaptic transmission, for which the mechanisms remain unclear. We hypothesized that increased presynaptic [Ca2+]i during transient OGD contributes to the depression of evoked field excitatory postsynaptic potentials (fEPSPs). Additionally, we hypothesized that increased buffering of intracellular calcium would shorten electrophysiological recovery after transient ischemia. Mouse hippocampal slices were exposed to 2 to 8 min of OGD. fEPSPs evoked by Schaffer collateral stimulation were recorded in the stratum radiatum, and whole cell current or voltage clamp recordings were performed in CA1 neurons. Transient ischemia led to increased presynaptic [Ca2+]i, (shown by calcium imaging), increased spontaneous miniature EPSP/Cs, and depressed evoked fEPSPs, partially mediated by adenosine. Buffering of intracellular Ca2+ during OGD by membrane-permeant chelators (BAPTA-AM or EGTA-AM) partially prevented fEPSP depression and promoted faster electrophysiological recovery when the OGD challenge was stopped. The blocker of BK channels, charybdotoxin (ChTX), also prevented fEPSP depression, but did not accelerate post-ischemic recovery. These results suggest that OGD leads to elevated presynaptic [Ca2+]i, which reduces evoked transmitter release; this effect can be reversed by increased intracellular Ca2+ buffering which also speeds recovery.
authors.affiliation: Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Shirin
authors.initials: S
authors.lastname: Jalini
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, ON, Canada.|Department of Biology, Loyola University Chicago, Chicago, IL, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Ye
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Tonkikh
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Milton P
authors.initials: MP
authors.lastname: Charlton
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Krembil Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Carlen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D018999:Charybdotoxin / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D051036:Large-Conductance Calcium-Activated Potassium Channels; D018999:Charybdotoxin; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C046770:EGTA acetoxymethyl ester; D002118:Calcium