Preconditioning improves function and recovery of single muscle fibers during severe hypoxia and reoxygenation.
Reperfusion following prolonged ischemia induces cellular damage in whole skeletal muscle models. Ischemic preconditioning attenuates the deleterious effects. We tested whether individual skeletal muscle fibers would be similarly affected by severe hypoxia and reoxygenation (H/R) in the absence of extracellular factors and whether cellular damage could be alleviated by hypoxic preconditioning. Force and free cytosolic Ca2+ ([Ca2+]c) were monitored in Xenopus single muscle fibers (n = 24) contracting tetanically at 0.2 Hz during 5 min of severe hypoxia and 5 min of reoxygenation. Twelve cells were preconditioned by a shorter bout of H/R 1 h before the experimental trial. In preconditioned cells, force relative to initial maximal values (P/P(o)) and relative peak [Ca2+]c fell (P < 0.05) during 5 min of hypoxia and recovered during reoxygenation. In contrast, P/P(o) and relative peak [Ca2+]c fell more during hypoxia (P < 0.05) and recovered less during reoxygenation (P < 0.05) in control cells. The ratio of force to [Ca2+]c was significantly higher in the preconditioned cells during severe hypoxia, suggesting that changes in [Ca2+]c were not solely responsible for the loss in force. We conclude that 1) isolated skeletal muscle fibers contracting in the absence of extracellular factors are susceptible to H/R injury associated with changes in Ca2+ handling; and 2) hypoxic preconditioning improves contractility, Ca2+ handling, and cell recovery during subsequent hypoxic insult.
Kohin
S
S
Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA. skohin@ucsd.edu
Stary
C M
CM
Howlett
R A
RA
Hogan
M C
MC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D005260:Female; D019194:Ischemic Preconditioning; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D014982:Xenopus laevis
D010100:Oxygen; D002118:Calcium