Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus.
A mild ischemic load applied after a lethal ischemic insult reduces the subsequent ischemia-reperfusion injury, and is called ischemic postconditioning (PostC). We studied the effect of ischemic PostC on synaptic glutamate release using a whole-cell patch-clamp technique. We recorded spontaneous exc...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2019-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0215104 |
id |
doaj-7c6078898837453fb2e03d5544f5a66b |
---|---|
record_format |
Article |
spelling |
doaj-7c6078898837453fb2e03d5544f5a66b2021-03-03T20:44:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01144e021510410.1371/journal.pone.0215104Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus.Shohei YokoyamaIchiro NakagawaYoichi OgawaYudai MorisakiYasushi MotoyamaYoung Su ParkYasuhiko SaitoHiroyuki NakaseA mild ischemic load applied after a lethal ischemic insult reduces the subsequent ischemia-reperfusion injury, and is called ischemic postconditioning (PostC). We studied the effect of ischemic PostC on synaptic glutamate release using a whole-cell patch-clamp technique. We recorded spontaneous excitatory post-synaptic currents (sEPSCs) from CA1 pyramidal cells in mouse hippocampal slices. The ischemic load was perfusion of artificial cerebrospinal fluid (ACSF) equilibrated with mixed gas (95% N2 and 5% CO2). The ischemic load was applied for 7.5 min, followed by ischemic PostC 30 s later, consisting of three cycles of 15 s of reperfusion and 15 s of re-ischemia. We found that a surging increase in sEPSCs frequency occurred during the immediate-early reperfusion period after the ischemic insult. We found a significant positive correlation between cumulative sEPSCs and the number of dead CA1 neurons (r = 0.70; p = 0.02). Ischemic PostC significantly suppressed this surge of sEPSCs. The mitochondrial KATP (mito-KATP) channel opener, diazoxide, also suppressed the surge of sEPSCs when applied for 15 min immediately after the ischemic load. The mito-KATP channel blocker, 5-hydroxydecanoate (5-HD), significantly attenuated the suppressive effect of both ischemic PostC and diazoxide application on the surge of sEPSCs. These results suggest that the opening of mito-KATP channels is involved in the suppressive effect of ischemic PostC on synaptic glutamate release and protection against neuronal death. We hypothesize that activation of mito-KATP channels prevents mitochondrial malfunction and breaks mutual facilitatory coupling between glutamate release and Ca2+ entry at presynaptic sites.https://doi.org/10.1371/journal.pone.0215104 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shohei Yokoyama Ichiro Nakagawa Yoichi Ogawa Yudai Morisaki Yasushi Motoyama Young Su Park Yasuhiko Saito Hiroyuki Nakase |
spellingShingle |
Shohei Yokoyama Ichiro Nakagawa Yoichi Ogawa Yudai Morisaki Yasushi Motoyama Young Su Park Yasuhiko Saito Hiroyuki Nakase Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus. PLoS ONE |
author_facet |
Shohei Yokoyama Ichiro Nakagawa Yoichi Ogawa Yudai Morisaki Yasushi Motoyama Young Su Park Yasuhiko Saito Hiroyuki Nakase |
author_sort |
Shohei Yokoyama |
title |
Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus. |
title_short |
Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus. |
title_full |
Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus. |
title_fullStr |
Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus. |
title_full_unstemmed |
Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus. |
title_sort |
ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial atp-dependent potassium channels in the mouse hippocampus. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
A mild ischemic load applied after a lethal ischemic insult reduces the subsequent ischemia-reperfusion injury, and is called ischemic postconditioning (PostC). We studied the effect of ischemic PostC on synaptic glutamate release using a whole-cell patch-clamp technique. We recorded spontaneous excitatory post-synaptic currents (sEPSCs) from CA1 pyramidal cells in mouse hippocampal slices. The ischemic load was perfusion of artificial cerebrospinal fluid (ACSF) equilibrated with mixed gas (95% N2 and 5% CO2). The ischemic load was applied for 7.5 min, followed by ischemic PostC 30 s later, consisting of three cycles of 15 s of reperfusion and 15 s of re-ischemia. We found that a surging increase in sEPSCs frequency occurred during the immediate-early reperfusion period after the ischemic insult. We found a significant positive correlation between cumulative sEPSCs and the number of dead CA1 neurons (r = 0.70; p = 0.02). Ischemic PostC significantly suppressed this surge of sEPSCs. The mitochondrial KATP (mito-KATP) channel opener, diazoxide, also suppressed the surge of sEPSCs when applied for 15 min immediately after the ischemic load. The mito-KATP channel blocker, 5-hydroxydecanoate (5-HD), significantly attenuated the suppressive effect of both ischemic PostC and diazoxide application on the surge of sEPSCs. These results suggest that the opening of mito-KATP channels is involved in the suppressive effect of ischemic PostC on synaptic glutamate release and protection against neuronal death. We hypothesize that activation of mito-KATP channels prevents mitochondrial malfunction and breaks mutual facilitatory coupling between glutamate release and Ca2+ entry at presynaptic sites. |
url |
https://doi.org/10.1371/journal.pone.0215104 |
work_keys_str_mv |
AT shoheiyokoyama ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus AT ichironakagawa ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus AT yoichiogawa ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus AT yudaimorisaki ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus AT yasushimotoyama ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus AT youngsupark ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus AT yasuhikosaito ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus AT hiroyukinakase ischemicpostconditioningpreventssurgeofpresynapticglutamatereleasebyactivatingmitochondrialatpdependentpotassiumchannelsinthemousehippocampus |
_version_ |
1714820777027567616 |