Physiological roles of hydrogen sulfide: Synaptic modulation, neuroprotection, and smooth muscle relaxation

Nearly 300 years have passed since the first description of the toxicity of hydrogen sulfide (H2S) in 1713. Although many studies have been devoted to its toxicity, very little attention has been paid to understanding its normal physiological function. Relatively high concentrations of endogenous H2S, however, have recently been discovered in animal tissues, and its possible function as a biological messenger has been proposed. H2S enhances the activity of N-methyl-D-aspartate receptors and facilitates the induction of hippocampal long-term potentiation, a synaptic model for memory. H2S also increases intracellular concentrations of Ca2+ in glia and induces Ca2+ waves, which mediate glial signal transmission. Based on accumulating evidence for the reciprocal interactions between glia and neurons, it has been suggested that glia modulate synaptic transmission. Therefore, H2S may regulate synaptic activity by modulating the activity of both neurons and glia. In addition to a role in the signal transduction, H2S protects neurons from oxidative stress and in smooth muscle it may function as a relaxant. H2S, the toxic gas, may therefore be used as a multifunctional signaling mechanism under normal physiological conditions.