Hydrogen Sulfide and T-Type Ca2+ Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion.

BACKGROUND: Hydrogen sulfide (H2S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H2S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Cav3.2 T-type Ca2+ channels mediate some of the biological activity of H2S, we focus on the role of the H2S/Cav3.2 pathway in regulating the neuronal and neuroendocrine function.

SUMMARY: In the neuronal system, H2S regulates the activity of various ion channels including Cav3.2. Exogenous and endogenous H2S enhances the Cav3.2 channel activity, promoting somatic and visceral pain signaling. The H2S/Cav3.2 pathway also facilitates neuritogenesis or neuronal differentiation. Interestingly, endogenous H2S formed by CSE regulates secretory function by enhancing Cav3.2 channel activity in neuroendocrine-differentiated prostate cancer cells or carotid glomus cells. Key Messages: The H2S/Cav3.2 pathway may serve as therapeutic targets for treatment of intractable pain, neuronal injury, androgen-independent prostate cancer, cardiovascular diseases, etc.