Ischemic Postconditioning Reduces NMDA Receptor Currents Through the Opening of the Mitochondrial Permeability Transition Pore and KATP Channel in Mouse Neurons
- 7 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Neurobiology
- Vol. 42 (4), 1079-1089
- https://doi.org/10.1007/s10571-020-00996-y
Abstract
Ischemic postconditioning (PostC) is known to reduce cerebral ischemia/reperfusion (I/R) injury; however, whether the opening of mitochondrial ATP-dependent potassium (mito-KATP) channels and mitochondrial permeability transition pore (mPTP) cause the depolarization of the mitochondrial membrane that remains unknown. We examined the involvement of the mito-KATP channel and the mPTP in the PostC mechanism. Ischemic PostC consisted of three cycles of 15 s reperfusion and 15 s re-ischemia, and was started 30 s after the 7.5 min ischemic load. We recorded N-methyl-d-aspartate receptors (NMDAR)-mediated currents and measured cytosolic Ca2+ concentrations, and mitochondrial membrane potentials in mouse hippocampal pyramidal neurons. Both ischemic PostC and the application of a mito-KATP channel opener, diazoxide, reduced NMDAR-mediated currents, and suppressed cytosolic Ca2+ elevations during the early reperfusion period. An mPTP blocker, cyclosporine A, abolished the reducing effect of PostC on NMDAR currents. Furthermore, both ischemic PostC and the application of diazoxide potentiated the depolarization of the mitochondrial membrane potential. These results indicate that ischemic PostC suppresses Ca2+ influx into the cytoplasm by reducing NMDAR-mediated currents through mPTP opening. The present study suggests that depolarization of the mitochondrial membrane potential by opening of the mito-KATP channel is essential to the mechanism of PostC in neuroprotection against anoxic injury.Keywords
Funding Information
- KAKENHI (JP16K10735)
This publication has 38 references indexed in Scilit:
- Ischemia-Reperfusion Injury in StrokeInterventional Neurology, 2012
- Ischemic Postconditioning as a Novel Avenue to Protect against Brain Injury after StrokeJournal of Cerebral Blood Flow & Metabolism, 2009
- Postconditioning with Isoflurane Reduced Ischemia-induced Brain Injury in RatsAnesthesiology, 2008
- Ischemic Postconditioning Protects Against Global Cerebral Ischemia/Reperfusion-Induced Injury in RatsStroke, 2008
- Postconditioning, a Series of Brief Interruptions of Early Reperfusion, Prevents Neurologic Injury After Spinal Cord IschemiaAnnals of Surgery, 2006
- Interrupting Reperfusion as a Stroke Therapy: Ischemic Postconditioning Reduces Infarct Size after Focal Ischemia in RatsJournal of Cerebral Blood Flow & Metabolism, 2006
- The effects of ischaemic preconditioning, diazoxide and 5‐hydroxydecanoate on rat heart mitochondrial volume and respirationJournal Of Physiology-London, 2002
- Calcium in Ischemic Cell DeathStroke, 1998
- Elevation of the Extracellular Concentrations of Glutamate and Aspartate in Rat Hippocampus During Transient Cerebral Ischemia Monitored by Intracerebral MicrodialysisJournal of Neurochemistry, 1984
- The uptake and extrusion of monovalent cations by isolated heart mitochondriaMolecular and Cellular Biochemistry, 1976