Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus
| Autor: | Yoichi Ogawa, Yudai Morisaki, Young Su Park, Ichiro Nakagawa, Shohei Yokoyama, Yasuhiko Saito, Hiroyuki Nakase, Yasushi Motoyama |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Potassium Channels Science Ischemia Hippocampus Glutamic Acid Myocardial Reperfusion Injury Pharmacology Hippocampal formation 03 medical and health sciences Mice 0302 clinical medicine Adenosine Triphosphate Diazoxide medicine Potassium Channel Blockers Animals Channel blocker Ischemic Postconditioning Neurons Multidisciplinary Chemistry Glutamate receptor Excitatory Postsynaptic Potentials medicine.disease Potassium channel Mitochondria Mice Inbred C57BL 030104 developmental biology Excitatory postsynaptic potential Medicine Hydroxy Acids Decanoic Acids 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | PLoS ONE, Vol 14, Iss 4, p e0215104 (2019) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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