Hydrogen sulfide and neuronal differentiation: Focus on Ca2+ channels

Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

“…Similar evidence for endogenous and exogenous H 2 S regulation of T-currents has been detected in Ca v 3.2-transfected HEK293 cells [9]. We consider that H 2 S interacts with Zn 2+ that binds to the His 191 residue of Ca v 3.2 and suppresses the channel function, leading to the facilitation of Ca v 3.2-dependent T-currents [24]. We have reported that H 2 S donors did not affect T-currents in Ca v 3.2-transfected HEK293 cells that abundantly express CSE, whereas the CSE inhibitor, PPG, suppressed the T-currents in the same cells [9].…”

“…One of the most interesting findings is the cyclic AMP-dependent upregulation of CSE and CBS, two major enzymes that generate H 2 S (see Fig. 3), known to enhance Ca v 3.2 channel functions [9,10,24]. The T-current facilitation by two distinct H 2 S donors, NaHS and Na 2 S, and its suppression by two distinct CSE inhibitors, PPG and b-cyano-Lalanine, but not the CBS inhibitor, aminooxyacetic acid (see Fig.…”

“…Among three isoforms of T-type Ca 2+ channels, Ca v 3.2 mediates the facilitation of somatic and visceral pain signals by H 2 S [7,8,15,16], and the increased activity of the H 2 S/Ca v 3.2 pathway is involved in neuropathic pain and in pancreatic and bladder nociception accompanying pancreatitis and cystitis, respectively [17][18][19][20][21]. The enhanced activity of Ca v 3.2 by NaHS, a donor of H 2 S, also causes neuronal differentiation characterized by neurite outgrowth and functional upregulation of high voltage-activated Ca 2+ channels in NG108-15 cells (mouse neuroblastoma  rat glioma hybrid cells) [22][23][24]. Of interest is that Ca v 3.2 plays a role in low-threshold exocytosis in neurons or endocrine secretory cells [25][26][27] including neuroendocrine-like differentiated prostate cancer cells [28].…”

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

“…In the nociceptor neurons, H 2 S enhances the function of Ca v 3.2 T-type Ca 2+ channels [8][9][10][11][12] and TRPA1 channels [13,14] , leading to the neuronal excitation and then pain sensation or hyperalgesia/allodynia [3,7,15] . We have also shown that the acceleration of Ca v 3.2 channel activity by exogenous H 2 S causes neuritogenesis and neuronal differentiation in NG108-15 cells [9,10,16] , and that the endogenous H 2 S/ Ca v 3.2 pathway regulates secretory function in the neuroendocrine-like differentiated human prostate cancer LNCaP cells [17] . Here, we thus focus on the roles of Ca v 3.2 T-type Ca 2+ channels and H 2 S in pain processing, neuronal differentiation and neuroendocrine secretion.…”

Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells

“…On the other hand, our group has reported that H 2 S enhances the function of Ca v 3.2 T-type calcium channels. 5,24,25) In addition, an independent group has reported the contribution of Ca v 3.2 to the cell proliferation of prostate cancer LNCaP cells. 26) However, the H 2 S/Ca v 3.2 pathway is not considered to be involved in the H 2 S-mediated proliferation of AGS cells, because we could not detect the T-type calcium channel-dependent currents in AGS cells by the whole cell patch clamp technique (data not shown).…”