New insights into molecular mechanism(s) underlying the presynaptic action of nitric oxide on GABA release

摘要: Abstract Background Nitric oxide (NO) is an important presynaptic modulator of synaptic transmission. Here, we aimed to correlate the release major inhibitory neurotransmitter GABA with intracellular events occurring in rat brain axon terminals during their exposure NO range nanomolar–low micromolar concentrations. Methods Using [3H]GABA and fluorescent dyes (Fluo 4-AM, acridine orange rhodamine 6G), following parameters were evaluated: vesicular cytosolic pools, calcium concentration, vesicle acidification, mitochondrial membrane potential. Diethylamine NONOate (DEA/NO) S-nitroso-N-acetylpenicillamine (SNAP) used as donors. Results DEA/NO SNAP (in presence dithiothreitol (DTT)) stimulated external Ca2 +-independent release, which was not attributed a rise concentration. coincided increasing level cytosol decreasing content available for exocytotic release. There strong temporal correlation between NO-induced increase [GABA] dissipation both proton gradient Dissipation reversible, recovery correlated time re-accumulation into vesicles. The molar ratio DTT determined rate duration processes. Conclusions We suggest that can stimulate via transporter reversal resulting from increased levels cytosol. latter reversible appears be due S-nitrosylation key proteins, affect energy status pre-synapse. General significance Our findings provide new insight molecular mechanism(s) underlying action nitric on neurotransmission.