Soluble adenylyl cyclase in the locus coeruleus

Although it has been demonstrated that the CO₂-sensitivity in the locus coeruleus (LC) is mediated by changes in pH, the involvement of HCO₃^- in the CO₂-detection mechanism in these neurons cannot be excluded. In the present work, we characterized sAC for the first time in the LC and we asked whether this enzyme is important in the detection of changes in HCO₃^-/CO₂ levels in these neurons, using an approach that allowed us to isolate CO₂ from pH stimulus. sAC mRNA expression and activity were upregulated from 0mM HCO₃^-/0% CO₂ to 24 mM HCO₃^-/5% CO₂ in the LC but not in the cortex of the brain. Comparing the effects of sAC and tmAC inhibitors in the LC, we observed that both tmAC and sAC contribute to the generation of cAMP during normocapnic conditions but only sAC contributed to the generation of cAMP during isohydric hypercapnia. Furthermore, activation of tmAC induced an increase in sAC expression in LC, but not cortex.sAC may be involved in CO₂ sensitivity in the LC, up to its threshold of saturation, with a particular contribution of this enzyme in situations when low HCO₃^- concentrations occur. Its role should be further explored in pathological states to determine whether sAC activation with HCO₃^- alters ventilation.