Abstract：
Reactive sulfur species including sulfides, polysulfides and cysteine hydropersulfide play extensive roles in health and disease, which involve modification of protein functions through the interaction with metals bound to the proteins, cleavage of cysteine disulfide (S-S) bonds and S-persulfidation of cysteine residues. Sulfides over a wide micromolar concentration range enhance the activity of Cav3.2 T-type Ca2+ channels by eliminating Zn2+ bound to the channels, thereby promoting somatic and visceral pain. Cav3.2 is under inhibition by Zn2+ in physiological conditions, so that sulfides function to reboot Cav3.2 from Zn2+ inhibition and increase the excitability of nociceptors. On the other hand, polysulfides generated from sulfides activate TRPA1 channels via cysteine S-persulfidation, thereby facilitating somatic, but not visceral, pain. Thus, Cav3.2 function enhancement by sulfides and TRPA1 activation by polysulfides, synergistically accelerate somatic pain signals. The increased activity of the sulfide/Cav3.2 system, in particular, appears to have a great impact on pathological pain, and may thus serve as a therapeutic target for treatment of neuropathic and inflammatory pain including visceral pain.
摘要：
反应性硫物质，包括硫化物，多硫化物和半胱氨酸氢过硫化物在健康和疾病中起着广泛的作用，涉及通过与结合到蛋白质上的金属的相互作用来修饰蛋白质功能，半胱氨酸二硫化物(S-S)键的裂解和半胱氨酸残基的S-过硫化。在很宽的微摩尔浓度范围内的硫化物通过消除与通道结合的Zn2来增强Cav3.2T型Ca2通道的活性，从而促进躯体和内脏疼痛。Cav3.2在生理条件下受到Zn2+的抑制,因此，硫化物可以从Zn2抑制作用中重新启动Cav3.2，并增加伤害感受器的兴奋性。另一方面,由硫化物产生的多硫化物通过半胱氨酸S-过硫化激活TRPA1通道，从而促进体细胞，但不是内脏，疼痛。因此，硫化物增强Cav3.2功能和多硫化物激活TRPA1，协同加速躯体疼痛信号。硫化物/Cav3.2系统的活性增加，特别是,似乎对病理性疼痛有很大的影响，并且因此可以用作治疗神经性和炎性疼痛(包括内脏疼痛)的治疗靶标。
