Cholinergic signaling is essential for hydrogen sulfide responses in Caenorhabditis elegans
Manbeck, Katherine Elizabeth
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Hydrogen sulfide, H2S, is one of three endogenously produced gaseous molecules that can act in cellular signaling. In the brain, H2S has proposed roles in modulating long-term potentiation, nociception, and neuroprotection. To further understand the impact of H2S on neurons, we conducted a candidate screen in Caenorhabditis elegans of neuronal factors to identify those involved in the normal response to H2S. Our studies show that cholinergic signaling is essential to survive exposure to H2S. We found animals with mutations in genes required for the biosynthesis and trafficking of acetylcholine died when exposed to H2S in conditions where wild-type animals survive. Our data further indicate that the levamisole-sensitive acetylcholine receptor subunit, unc-29, is involved in H2S signaling. Unexpectedly, we discovered that the requirement for unc-29 in H2S is abrogated by fasting or entry into dauer. The egl-2 ether-a-go-go potassium channel is involved in mediating the effects of fasting on the response to H2S. Together, our results suggest there are multiple neuronal responses to H2S that vary based on physiological context. Both H2S and cholinergic signaling have been implicated in neurodegenerative diseases, including Parkinson ’s disease. Our data suggest that understanding the interactions between cholinergic signaling and H2S could lead to new therapeutic strategies for these devastating diseases.