R. Vandenboom et Me. Houston, PHOSPHORYLATION OF MYOSIN AND TWITCH POTENTIATION IN FATIGUED SKELETAL-MUSCLE, Canadian journal of physiology and pharmacology, 74(12), 1996, pp. 1315-1321
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 mamma
lian skeletal muscle. Tetanic stimulation for 120 s reduced peak tetan
ic force (P-o) of mouse extensor digitorum longus (EDL) muscle by 74 /- 2%. Despite high frequency fatigue (HFF), P-t was potentiated by 18
+/- 3% when R-LC phosphorylation (in moles phosphate per mole R-LC) w
as increased from 0.11 +/- 0.05 (rest) to 0.52 +/- 0.04 by 15 s of sti
mulation. Thereafter P-t declined below resting values despite high le
vels for R-LC phosphorylation (0.80 +/- 0.04 after 120 s of stimulatio
n). In separate experiments, 10 min of stimulation, which reduced P-o
and P-t by 80 +/- 2 and 67 +/- 3%, respectively, was used to induce lo
w frequency fatigue (LFF) in mouse EDL muscle. During LFF, long-lastin
g reductions in P-t were evident despite near-normal levels for P-o (7
9 +/- 2 and 98 +/- 2% of controls, respectively). Application of condi
tioning stimuli (CS) increased R-LC phosphate content of fatigued musc
les from 0.15 +/- 0.03 (rest) to 0.56 +/- 0.03 (stimulated) and potent
iated P-t by 26 +/- 2% compared with LFF. Twitch potentiation during L
FF was transient, lasting only as long as R-LC was phosphorylated abov
e resting values for fatigued muscles. Overall, our data showing poten
tiated twitch forces concomitant with elevations in R-LC phosphate con
tent during either HFF or LFF of mouse EDL muscle suggest that this mo
lecular event counters reduced twitch forces during these forms of fat
igue. Our results may be explained by R-LC phosphorylation induced inc
reases in Ca2+ sensitivity for twitch force production in fatigued mus
cle.