Differential contributions of adenosine to hypoxia-evoked depressions of three neuronal pathways in isolated spinal cord of neonatal rats.

background and purposeHypoxic effects on neuronal functions vary significantly with experimental conditions, but the mechanism for this is unclear. Adenosine has been reported to play a key role in depression of neuronal activities in the CNS during acute hypoxia. Hence, we examined the effect of acute hypoxia on different spinal reflex potentials and the contribution of adenosine to them. EXPERIMENTAL APPROACH: Spinal reflex potentials, monosynaptic reflex potential (MSR), slow ventral root potential (sVRP) and dorsal root potential (DRP), were measured in the isolated spinal cord of the neonatal rat. Adenosine release was measured by using enzymatic biosensors. KEY

resultsIn the spinal cord preparation isolated from postnatal day 5-8 rats at 27°C, acute hypoxia induced adenosine release and depressed three reflex potentials. However, in postnatal day 0-3 rats at 27°C, the hypoxic-induced adenosine release and depression of MSR were negligible, while the depression of sVRP and DRP were perceptible responses. In postnatal day 0-3 rats at 33°C, hypoxia evoked adenosine release and depression of MSR. An adenosine A(1) receptor selective antagonist and a high [Ca(2+)](o), which suppressed adenosine release, abolished the hypoxic-induced depression of MSR but not those of sVRP and DRP. CONCLUSIONS AND IMPLICATIONS: Hypoxic-induced depression of MSR depends on adenosine release, which is highly susceptible to age, temperature and [Ca(2+)](o). However, a large part of the depressions of DRP and sVRP are mediated via adenosine-independent mechanisms. This differential contribution of adenosine to depression is suggested to be an important factor for the variable effects of hypoxia on neuronal functions.