Nitric oxide contributes to irreversible membrane dysfunction caused by experimental ischemia in rat hippocampal CA1 neurons.
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.
Onitsuka
M
M
Department of Physiology, Kurume University School of Medicine, Kurume-shi, Japan.
Mihara
S
S
Yamamoto
S
S
Shigemori
M
M
Higashi
H
H
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
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