Hydrogen sulfide and neuronal differentiation: Focus on Ca2+ channels

Abstract

Hydrogen sulfide (H2S) is considered the third gasotransmitter following nitric oxide (NO) and carbon monoxide (CO) in the mammalian body including the brain, heart, blood vessels, liver, kidney, pancreas, lung, gastrointestinal tract and reproductive organs. H2S is formed endogenously from L-cysteine by multiple enzymes, such as cystathionine-γ-lyase, cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase, and participates in a variety of biological events through a number of target molecules. Exogenous and/or endogenous H2S enhances the activity of T-type Ca2+ channels in NG108-15 cells and isolated dorsal root ganglion neurons that abundantly express Cav3.2, and in Cav3.2-transfected HEK293 cells. Cav3.2 mediates not only the H2S-induced enhancement of pain signals in nociceptor neurons, but also neuronal differentiation characterized by neuritogenesis and functional upregulation of high voltage-activated Ca2+ channels in NG108-15 cells. In this review, we focus on the functional modulation by H2S of primarily Cav3.2 T-type Ca2+ channels and the molecular mechanisms underlying the H2S-induced neuronal differentiation.