Secretion of Interleukin 6 in Human Skeletal Muscle Cultures Depends on Ca2+ Signalling

The systemic effects of physical activity are mediated by the release IL-6 and other myokines from contracting muscle. Although muscle has been extensively studied, information on cellular mechanisms is fragmentary scarce, especially regarding role Ca2+ signals. aim this study was to characterize main components signals in human skeletal cells during secretion stimulated mobilizing agonist ATP. Primary cultures were prepared surgical samples, fluorescence microscopy used evaluate into medium determined using ELISA. Intracellular calcium chelator Bapta, low extracellular channels blocker La3+ reduced ATP-stimulated, but not basal secretion. Secretion inhibited blockers L-type (nifedipine, verapamil), T-type (NNC55-0396) Orai1 (Synta66) silencing expression. same effect achieved with inhibitors ryanodine receptors (ryanodine, dantrolene) IP3 (xestospongin C, 2-APB, caffeine). Inhibitors calmodulin (calmidazolium) calcineurin (FK506) also decreased transcription response ATP affected Bapta or T channel blocker. Our results prove that ATP-stimulated at post-transcriptional level signals, including mobilization stores, activation store-operated entry, subsequent voltage-operated calmodulin/calcineurin pathways.