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Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state

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Abstract

Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (KATP) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoKATP channels). K+ channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study. Nicorandil (10 μM), improved the muscle function reversing fatigue as increased post-fatigue tension in the peak and total tension significantly with respect to the fatigued condition. However, this beneficial effect was prevented by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD, 500 μM) and by the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 1 mM), but not by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM). Nicorandil also decreased lipid peroxidation and maintained both reduced glutathione (GSH) levels and an elevated GSH/GSSG ratio, whereas total glutathione (TGSH) remained unaltered during post-fatigue tension. In addition, NO production, measured through nitrite concentrations was significantly increased with nicorandil during post-fatigue tension; this increase remained unaltered in the presence of nicorandil plus L-NAME, nonetheless, this effect was reversed with nicorandil plus MPG. Hence, these results suggest that nicorandil improves the muscle function reversing fatigue in slow skeletal muscle fibers of chicken through its effects not only as a mitoKATP channel opener but also as NO donor and as an antioxidant.

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Acknowledgements

We thank to Universidad de Colima, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH) and Consejo Nacional de de Ciencia yTecnologia (CONACyT) the partial financial of this research. ESD was a receipient of a CONACyT PhD fellow. We acknowledge the partial financing to Coordinación de la Investigación Científica of UMSNH: CCR-CIC1821440; ASM-CIC-2.16; RMP-CIC 182171.

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RMP, XT, ASM, CCR, GC, LH, MH (Conceived and designed study, Contributed with new methods).

ESD, RMP, XT (Performed research, Analyzed data).

ESD, RMP, XT, CCR (Wrote the paper).

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Sánchez-Duarte, E., Trujillo, X., Cortés-Rojo, C. et al. Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state. J Bioenerg Biomembr 49, 159–170 (2017). https://doi.org/10.1007/s10863-016-9692-6

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