title: Chemical preconditioning prevents paradoxical increase in glutamate release during ischemia by activating ATP-dependent potassium channels in gerbil hippocampus.
abstract: Ischemic tolerance induced by pretreatment with a low dose of 3-nitropropionic acid (3-NPA), called chemical preconditioning, prolongs the delay to hypoxic depolarization and improves the recovery of synaptic transmission (Exp. Neurol. 166 (2000), 385-391). We studied the effect of chemical preconditioning on the presynaptic site by analyzing spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs) with a whole cell patch-clamp technique in gerbil hippocampal slices. The frequency of sEPSCs decreased first and then dramatically increased during ischemia (10 min in duration, low pO(2), and deprivation of glucose) up to 200-300%. This increase was apparently a paradox, since synaptic transmission evoked by electrical stimulation diminished when the sEPSC frequency started to increase. The frequency of mEPSCs also increased in the same time course. Increases in sEPSC and mEPSC frequencies were prevented by chemical preconditioning with 3-NPA (4 mg/kg) administered intraperitoneally 3 h before the preparation of brain slices. These effects of chemical preconditioning were abolished by glibenclamide (5 microM), a blocker of ATP-dependent potassium (K(ATP)) channels, applied in vitro before the ischemic insult. The application of diazoxide (500 microM), an opener of K(ATP) channels, produced the same preventive effects on sEPSC and mEPSC frequencies. These results suggested that chemical preconditioning acted on presynaptic terminals to prevent the paradoxical increase in glutamate release during ischemia through the activation of K(ATP) channels.
authors.affiliation: Department of Neurosurgery, Nara Medical University, Shijo-cho 840, Kashihara 634-8521, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakagawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Noriyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Sakaki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology* / Q000517:prevention & control*; D002118:Calcium / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005849:Gerbillinae; D018698:Glutamic Acid / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*
chemical_list: D009498:Neurotoxins; D009574:Nitro Compounds; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011422:Propionates; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D003981:Diazoxide; C015392:3-nitropropionic acid; D005905:Glyburide; D002118:Calcium