Prolonged force depression after mechanically demanding contractions is largely independent of Ca 2+ and reactive oxygen species

• Published in: The FASEB journal Vol. 31; no. 11; pp. 4809 - 4820
• Main Authors: Kamandulis, Sigitas, de Souza Leite, Felipe, Hernández, Andres, Katz, Abram, Brazaitis, Marius, Bruton, Joseph D, Venckunas, Tomas, Masiulis, Nerijus, Mickeviciene, Dalia, Eimantas, Nerijus, Subocius, Andrejus, Rassier, Dilson E, Skurvydas, Albertas, Ivarsson, Niklas, Westerblad, Håkan
• Format: Journal Article
• Language: English
• Published: United States 01-11-2017
• Subjects: Adult; Animals; Calcium - metabolism; Humans; Male; Mice; Muscle Contraction - physiology; Muscle Strength - physiology; Muscle, Skeletal - physiology; Reactive Oxygen Species - metabolism; Ryanodine Receptor Calcium Release Channel - metabolism; muscle damage; aging; eccentric contractions
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201700019R

Increased production of reactive oxygen/nitrogen species (ROS) and impaired cellular Ca
handling are implicated in the prolonged low-frequency force depression (PLFFD) observed in skeletal muscle after both metabolically and mechanically demanding exercise. Metabolically demanding high-intensity exercise can induce PLFFD accompanied by ROS-dependent fragmentation of the sarcoplasmic reticulum Ca
release channels, the ryanodine receptor 1s (RyR1s). We tested whether similar changes occur after mechanically demanding eccentric contractions. Human subjects performed 100 repeated drop jumps, which require eccentric knee extensor contractions upon landing. This exercise caused a major PLFFD, such that maximum voluntary and electrically evoked forces did not recover within 24 h. Drop jumps induced only minor signs of increased ROS, and RyR1 fragmentation was observed in only 3 of 7 elderly subjects. Also, isolated mouse muscle preparations exposed to drop-jump-mimicking eccentric contractions showed neither signs of increased ROS nor RyR1 fragmentation. Still, the free cytosolic [Ca
] during tetanic contractions was decreased by ∼15% 1 h after contractions, which can explain the exaggerated force decrease at low-stimulation frequencies but not the major frequency-independent force depression. In conclusion, PLFFD caused by mechanically demanding eccentric contractions does not involve any major increase in ROS or RyR1 fragmentation.-Kamandulis, S., de Souza Leite, F., Hernandez, A., Katz, A., Brazaitis, M., Bruton, J. D., Venckunas, T., Masiulis, N., Mickeviciene, D., Eimantas, N., Subocius, A., Rassier, D. E., Skurvydas, A., Ivarsson, N., Westerblad, H. Prolonged force depression after mechanically demanding contractions is largely independent of Ca
and reactive oxygen species.