Hydrogen sulfide pathway and skeletal muscle: an introductory review

The presence of the H₂ S pathway in skeletal muscle (SKM) has recently been established. SKM expresses the three constitutive H₂ S-generating enzymes in animals and humans, and it actively produces H₂ S. The main, recognized molecular targets of H₂ S, that is, potassium channels and PDEs, have been evaluated in SKM physiology in order to hypothesize a role for H₂ S signalling. SKM dysfunctions, including muscular dystrophy and malignant hyperthermia, have also been evaluated as conditions in which the H₂ S and transsulfuration pathways have been suggested to be involved. The intrinsic complexity of the molecular mechanisms involved in excitation-contraction (E-C) coupling together with the scarcity of preclinical models of SKM-related disorders have hampered any advances in the knowledge of SKM function. Here, we have addressed the role of the H₂ S pathway in E-C coupling and the relative importance of cystathionine β-synthase, cistathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase in SKM diseases.