Journal
JOURNAL OF NEUROSCIENCE
Volume 21, Issue 10, Pages 3515-3520Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.21-10-03515.2001
Keywords
long-term potentiation; oxyhemoglobin; Zn-protoporphyrin-IX; ondansetron; L-NOARG; 5-HT3 receptor; nitric oxide; heme oxygenase
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Funding
- NHLBI NIH HHS [1K14HL02478] Funding Source: Medline
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Carbon monoxide (CO), produced in the body by the enzyme heme oxygenase (HO), has been suggested as a retrograde synaptic messenger with a prominent role in the long- term potentiation (LTP) of certain areas of the brain. LTP of sympathetic ganglia is 5-HT3 receptor-dependent and has been shown to require nitric oxide for the maintenance, but not for the induction, phase. We investigated the possibility of CO being required for the induction of ganglionic LTP. Pretreatment of rat isolated superior cervical ganglia with oxyhemoglobin (25- 100 muM) completely blocked LTP. In the same ganglia, prolonged washout of oxyhemoglobin did not uncover any potentiation of the compound action potential. Oxyhemoglobin had no significant effect on the maintenance phase in ganglia with established LTP. Pretreatment of ganglia with the HO inhibitor zinc protoporphyrin- IX (ZnPP) (10 muM) completely and irreversibly prevented the expression of tetanus- evoked LTP. However, in the same ganglia, after superfusion of CO in the presence of ZnPP, tetanic stimulation readily evoked LTP. No effect was seen on the maintenance phase when ZnPP was superfused on ganglia with established LTP. Pretreatment of ganglia with the 5-HT3 receptor antagonist ondansetron (0.4 muM) alone completely and irreversibly blocked LTP. However, in the presence of CO, ondansetron did not block LTP. These results suggest that activation of 5-HT3 receptors may be involved in the production of CO. The results also suggest that CO, probably originating outside the presynaptic nerve terminal, is involved in the induction of LTP.
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