Nitric oxide and carbon monoxide activate locus coeruleus neurons through a cGMP-dependent protein kinase: involvement of a nonselective cationic channel

摘要: Nitric oxide (NO) and carbon monoxide (CO) have been identified as two diffusible signaling messengers in the brain, capable of stimulating soluble guanylate cyclase. Locus coeruleus (LC) is rich alpha 1 beta subunits Therefore, possible role cGMP pathway regulation LC neurons was investigated with electrophysiological techniques rat brain slices. Bath application various NO donors or CO-containing solutions increased firing rate most neurons. This activation reversed by scavenger hemoglobin, but not methemoglobin. intracellular selective activators cGMP-dependent protein kinase also caused increases cell rate. The actions were mutually occlusive H8, an inhibitor kinase. Hemoglobin H8 reduced neurons, no change found inhibitors synthase. In whole-cell recordings, effect associated inward current increase input conductance (mean reversal potential = -27 mV); these effects abolished using a low- sodium buffer. Spontaneous EPSCs cells modified donor administration. Taken together, data suggest that CO activate noradrenergic via nonselective cationic channel. It proposed occur at postsynaptic level there may be tonic neuronal pathway.