Ka. Alkadhi et al., Retrograde carbon monoxide is required for induction of long-term potentiation in rat superior cervical ganglion, J NEUROSC, 21(10), 2001, pp. 3515-3520
Carbon monoxide (CO), produced in the body by the enzyme heme oxygenase (HO
), has been suggested as a retrograde synaptic messenger with a prominent r
ole 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 r
equire nitric oxide for the maintenance, but not for the induction, phase.
We investigated the possibility of CO being required for the induction of g
anglionic LTP. Pretreatment of rat isolated superior cervical ganglia with
oxyhemoglobin (25- 100 muM) completely blocked LTP. In the same ganglia, pr
olonged washout of oxyhemoglobin did not uncover any potentiation of the co
mpound action potential. Oxyhemoglobin had no significant effect on the mai
ntenance phase in ganglia with established LTP. Pretreatment of ganglia wit
h the HO inhibitor zinc protoporphyrin- IX (ZnPP) (10 muM) completely and i
rreversibly prevented the expression of tetanus- evoked LTP. However, in th
e same ganglia, after superfusion of CO in the presence of ZnPP, tetanic st
imulation readily evoked LTP. No effect was seen on the maintenance phase w
hen ZnPP was superfused on ganglia with established LTP. Pretreatment of ga
nglia with the 5-HT3 receptor antagonist ondansetron (0.4 muM) alone comple
tely and irreversibly blocked LTP. However, in the presence of CO, ondanset
ron did not block LTP. These results suggest that activation of 5-HT3 recep
tors may be involved in the production of CO. The results also suggest that
CO, probably originating outside the presynaptic nerve terminal, is involv
ed in the induction of LTP.