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1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, and 3 Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44109; and 2 Department of Medicine, Medical College of Georgia, Augusta, Georgia 30912
Reactive oxygen
species contribute to diaphragm dysfunction in certain
pathophysiological conditions (i.e., sepsis and fatigue). However, the precise alterations induced by reactive oxygen species or
the specific species that are responsible for the derangements in
skeletal muscle function are incompletely understood. In this study, we
evaluated the effect of the superoxide anion radical (O2
·), hydroxyl radical (·OH), and hydrogen
peroxide (H2O2) on maximum calcium-activated
force (Fmax) and calcium sensitivity of the contractile
apparatus in chemically skinned (Triton X-100) single rat diaphragm
fibers. O2
· was generated using the
xanthine/xanthine oxidase system; ·OH was generated using 1 mM
FeCl2, 1 mM ascorbate, and 1 mM
H2O2; and H2O2 was
added directly to the bathing medium. Exposure to O2
· or ·OH significantly decreased
Fmax by 14.5% (P < 0.05) and 43.9%
(P < 0.005), respectively. ·OH had no effect on
Ca2+ sensitivity. Neither 10 nor 1,000 µM
H2O2 significantly altered Fmax or
Ca2+ sensitivity. We conclude that the diaphragm is
susceptible to alterations induced by a direct effect of ·OH and
O2
·, but not H2O2, on the
contractile proteins, which could, in part, be responsible for
prolonged depression in contractility associated with respiratory
muscle dysfunction in certain pathophysiological conditions.
free radicals; reactive oxygen species; skinned muscle fibers; respiratory muscle; skeletal muscle
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