PMID- 26934214
OWN - NLM
STAT- MEDLINE
DCOM- 20160726
LR  - 20190219
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 3
DP  - 2016
TI  - Raised Intracellular Calcium Contributes to Ischemia-Induced Depression of Evoked 
      Synaptic Transmission.
PG  - e0148110
LID - 10.1371/journal.pone.0148110 [doi]
LID - e0148110
AB  - 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.
FAU - Jalini, Shirin
AU  - Jalini S
AD  - Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, 
      Canada.
AD  - Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
FAU - Ye, Hui
AU  - Ye H
AD  - Krembil Research Institute, University Health Network, Toronto, ON, Canada.
AD  - Department of Biology, Loyola University Chicago, Chicago, IL, United States of 
      America.
FAU - Tonkikh, Alexander A
AU  - Tonkikh AA
AD  - Krembil Research Institute, University Health Network, Toronto, ON, Canada.
FAU - Charlton, Milton P
AU  - Charlton MP
AD  - Department of Physiology, University of Toronto, Toronto, ON, Canada.
FAU - Carlen, Peter L
AU  - Carlen PL
AD  - Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
AD  - Krembil Research Institute, University Health Network, Toronto, ON, Canada.
LA  - eng
GR  - MGP-37773/Canadian Institutes of Health Research/Canada
GR  - MOP 69045/Canadian Institutes of Health Research/Canada
GR  - MOP-82827/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160302
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chelating Agents)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 115422-61-2 (Charybdotoxin)
RN  - 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid 
      acetoxymethyl ester)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 99590-86-0 (EGTA acetoxymethyl ester)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*metabolism/physiopathology
MH  - Calcium/*metabolism
MH  - Charybdotoxin/pharmacology
MH  - Chelating Agents/pharmacology
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Evoked Potentials/drug effects/*physiology
MH  - Excitatory Postsynaptic Potentials/drug effects/*physiology
MH  - Hippocampus/drug effects/*metabolism/physiopathology
MH  - Large-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors
MH  - Mice
MH  - Neurons/drug effects/metabolism
PMC - PMC4775070
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/03/05 06:00
MHDA- 2016/07/28 06:00
PMCR- 2016/03/02
CRDT- 2016/03/03 06:00
PHST- 2014/12/03 00:00 [received]
PHST- 2016/01/13 00:00 [accepted]
PHST- 2016/03/03 06:00 [entrez]
PHST- 2016/03/05 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
PHST- 2016/03/02 00:00 [pmc-release]
AID - PONE-D-14-54257 [pii]
AID - 10.1371/journal.pone.0148110 [doi]
PST - epublish
SO  - PLoS One. 2016 Mar 2;11(3):e0148110. doi: 10.1371/journal.pone.0148110. 
      eCollection 2016.