title: Nitric oxide contributes to irreversible membrane dysfunction caused by experimental ischemia in rat hippocampal CA1 neurons.
abstract: The effects of agents which affect the action of nitric oxide (NO) were studied intracellularly on the ischemia-induced changes in membrane potential of single CA1 pyramidal neurons of the rat hippocampal slice preparations. The N-methyl-D-aspartate (NMDA) receptor antagonists, (+/-)-2-amino-5-phosphonopentanoic acid (AP5, 250 microM) or Co2 (2 mM) restored the membrane potential in more than 80% of the neurons. In about 60% of the neurons, the membrane potential was partially recovered as a result of exposure to the NO synthase inhibitor, NG-nitro-L-arginine (100 microM). The NO scavengers, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO, 300 microM) and hemoglobin (10 microM) restored the membrane potential in all neurons examined. Superoxide dismutase (50 U/ml) protected about 75% of the neurons from irreversible membrane dysfunction. It is concluded that the release of NO induced by experimental ischemia may result in the irreversible membrane dysfunction, and that a NO scavenger, carboxy-PTIO, prevents the ischemic changes in membrane potential. With respect to ischemic brain damage, the neuroprotection provided by carboxy-PTIO may have clinical relevance in the management of a variety of neurological conditions.
authors.affiliation: Department of Physiology, Kurume University School of Medicine, Kurume-shi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Onitsuka
authors.forename: S
authors.initials: S
authors.lastname: Mihara
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Shigemori
authors.forename: H
authors.initials: H
authors.lastname: Higashi
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D000860:Hypoxia; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D001565:Benzoates; D006454:Hemoglobins; D007093:Imidazoles; D016194:Receptors, N-Methyl-D-Aspartate; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D019335:Nitroarginine; D009569:Nitric Oxide; D003035:Cobalt; D015763:2-Amino-5-phosphonovalerate; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005947:Glucose