Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Glutamic Acid/*metabolism ; Hippocampus/*metabolism ; Ischemic Postconditioning/*methods ; Mitochondria/*metabolism ; Myocardial Reperfusion Injury/*prevention & control ; Neurons/*metabolism ; Potassium Channels/*metabolism; Adenosine Triphosphate/metabolism ; Animals ; Decanoic Acids/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Hippocampus/drug effects ; Hippocampus/pathology ; Hydroxy Acids/pharmacology ; Mice ; Mice, Inbred C57BL ; Mitochondria/drug effects ; Mitochondria/pathology ; Myocardial Reperfusion Injury/metabolism ; Myocardial Reperfusion Injury/pathology ; Neurons/drug effects ; Neurons/pathology ; Potassium Channel Blockers/pharmacology ; Potassium Channels/chemistry

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.
Competing Interests: The authors have declared that no competing interests exist.

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0 (Decanoic Acids)
0 (Hydroxy Acids)
0 (Potassium Channel Blockers)
0 (Potassium Channels)
0 (mitochondrial K(ATP) channel)
3KX376GY7L (Glutamic Acid)
624-00-0 (5-hydroxydecanoic acid)
8L70Q75FXE (Adenosine Triphosphate)

Date Created: 20190413 Date Completed: 20191230 Latest Revision: 20200309

20240829

PMC6461229

10.1371/journal.pone.0215104

30978206