title: Ryanodine receptors contribute to the induction of ischemic tolerance.
abstract: Ischemic tolerance (IT) is induced by a variety of insults to the brain (e.g., nonfatal ischemia, heat and hypoxia) and it provides a strong neuroprotective effect. Although the mechanisms are still not fully elucidated, Ca(2+) is regarded as a key mediator of IT. Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca(2+) from intracellular stores. In brain, neuronal RyRs are thought to play a role in various neuropathological conditions, including ischemia. The purpose of the present study was to investigate the involvement of RyRs in IT. Pretreatment with a RyR antagonist, dantrolene (25mg/kg, i.p), blocked IT in a gerbil global ischemia model, while a RyR agonist, caffeine (100mg/kg, i.p), stimulated the production of IT. In vitro, using rat hippocampal cells, short-term oxygen/glucose deprivation induced preconditioning and RyR antagonists, dantrolene (50 and 100 μM) and ryanodine (100 and 200 μM) prevented it. RyR protein and mRNA levels were transiently decreased after induction of IT. These results suggest that RyRs are involved in the induction of ischemic tolerance.
authors.affiliation: Department of Physiology2, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan; Department of Molecular Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Nakamura-Maruyama
authors.affiliation: Department of Physiology2, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyamoto
authors.affiliation: Department of Physiology2, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Okabe
authors.affiliation: Department of Physiology2, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Himi
authors.affiliation: Department of Physiology2, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Lu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Physiology2, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Narita
authors.affiliation: Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Department of Molecular Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. Electronic address: tanakamu@kms.ac.jp.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D002118:Calcium
keywords: CA1 hippocampal cells; Cell culture; Intracellular Ca(2+); Ischemic tolerance; Oxygen glucose deprivation; Ryanodine receptor