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) wer e 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 mu M) or Co2+ (2 mM) restored the membrane potential in more than 80% of the neurons. In ab out 60% of the neurons, the membrane potential was partially recovered as a result of exposure to the NO synthase inhibitor, N-G-nitro-L-arg inine (100 mu M). The NO scavengers, enyl-4,4,5,5-tetramethylimidazoli ne-1-oxyl-3-oxide (carboxy-PTIO, 300 mu M) and hemoglobin (10 mu M) re stored the membrane potential in all neurons examined. Superoxide dism utase (50 U/ml) protected about 75% of the neurons from irreversible m embrane dysfunction. It is concluded that the release of NO induced by experimental ischemia may result in the irreversible membrane dysfunc tion, and that a NO scavenger, carboxy-PTIO, prevents the ischemic cha nges 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. (C) 1998 El sevier Science Ireland Ltd. All rights reserved.