Phosphorylation of myosin and twitch potentiation in fatigued skeletal muscle.
Phosphorylation of myosin regulatory light chain (R-LC) increases the sensitivity of skinned skeletal muscle fibers to low Ca2+ activation. The purpose of this study was to determine whether phosphorylation of R-LC-mediated increases in Ca2+ sensitivity provides a molecular basis for potentiated twitch forces observed during fatigue of intact mammalian skeletal muscle. Tetanic stimulation for 120 s reduced peak tetanic force (Po) of mouse extensor digitorum longus (EDL) muscle by 74 +/- 2%. Despite high frequency fatigue (HFF), Pt was potentiated by 18 +/- 3% when R-LC phosphorylation (in moles phosphate per mole R-LC) was increased from 0.11 +/- 0.05 (rest) to 0.52 +/- 0.04 by 15 s of stimulation. Thereafter Pt declined below resting values despite high levels for R-LC phosphorylation (0.80 +/- 0.04 after 120 s of stimulation). In separate experiments, 10 min of stimulation, which reduced Po and Pt by 80 +/- 2 and 67 +/- 3%, respectively, was used to induce low frequency fatigue (LFF) in mouse EDL muscle. During LFF, long-lasting reductions in Pt were evident despite near-normal levels for Po (79 +/- 2 and 98 +/- 2% of controls, respectively). Application of conditioning stimuli (CS) increased R-LC phosphate content of fatigued muscles from 0.15 +/- 0.03 (rest) to 0.56 +/- 0.03 (stimulated) and potentiated Pt by 26 +/- 2% compared with LFF. Twitch potentiation during LFF was transient, lasting only as long as R-LC was phosphorylated above resting values for fatigued muscles. Overall, our data showing potentiated twitch forces concomitant with elevations in R-LC phosphate content during either HFF or LFF of mouse EDL muscle suggest that this molecular event counters reduced twitch forces during these forms of fatigue. Our results may be explained by R-LC phosphorylation induced increases in Ca2+ sensitivity for twitch force production in fatigued muscle.
Vandenboom
R
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Department of Kinesiology, University of Waterloo, ON, Canada.
Houston
M E
ME
D000818:Animals; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018763:Muscle Fatigue / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation
D018994:Myosin Light Chains; D009218:Myosins