P62: Hydrogen sulfide in regulation of synaptic transmission

Abstract

The role of H2S in regulation of synaptic transmission was studied using electrophysiological and fluorescent methods. In frog and mouse neuromuscular junctions (NMJ) NaHS increased spontaneous and evoked transmitter release in response to single stimuli. During high-frequency stimulation NaHS decreased the depression of end-plate potential amplitudes (EPPs) in frog NMJ and increased the decay of EPPs amplitudes in mouse NMJ. Using the fluorescent dye FM 1–43 we found that NaHS had opposite effects endocytosis of synaptic vesicles during high-frequency stimulation in frog (increased endocytosis) and mouse (decreased endocytosis) motor nerve endings. It was concluded that H2S accelerated the recycling of synaptic vesicles in frog nerve endings during high-frequency stimulation. In mouse NMJ the increase of exocytosis followed by the decrease in endocytosis leads to more pronounced depression of EPPs. The analysis of intracellular mechanisms revealed that H2S activated ryanodine receptors and increased intracellular Ca2+ concentrations in motor nerve ending. In frog and mouse NMJ L-cysteine increased evoked transmitter release similar to H2S and inhibition of CSE or CBS decreased acetylcholine release, suggesting that endogenous H2S modulates synaptic transmission. Using RT PCR we found expression of mRNA of CSE and CBS in mouse diaphragm. We conclude, H2S is synthesized in frog and mouse NMJ and acts to modulate transmitter release. In further experiments using hippocampal slices of neonatal rats it was shown that NaHS influenced the neuronal network activity. NaHS dose-dependently inhibited giant depolarizing potentials affecting GABA–evoked responses without influence on spontaneous GABA-currents.