Dynamics of Myosin-Driven Skeletal Muscle Contraction: I. Steady-State Force Generation

The role of phosphorylation of the myosin regulatory light chains (RLC) is well established in smooth muscle contraction, but in striated (skeletal and cardiac) muscle its role is still controversial. We have studied the effects of RLC phosphorylation in reconstituted myosin and in skinned skeletal muscle fibers where Ca2+sensitivity and the kinetics of steady-state force development were measured. Skeletal muscle myosin reconstituted with phosphorylated RLC produced a much higher Ca2+sensitivity of thin filament-regulated ATPase activity than nonphosphorylated RLC (change in −log of the Ca2+concentration producing half-maximal activation = ∼0.25). The same was true for the Ca2+sensitivity of force in skinned skeletal muscle fibers, which increased on reconstitution of the fibers with the phosphorylated RLC. In addition, we have shown that the level of endogenous RLC phosphorylation is a crucial determinant of the Ca2+sensitivity of force development. Studies of the effects of RLC phosphorylation on the kinetics of force activation with the caged Ca2+, DM-nitrophen, showed a slight increase in the rates of force development with low statistical significance. However, an increase from 69 to 84% of the initial steady-state force was observed when nonphosphorylated RLC-reconstituted fibers were subsequently phosphorylated with exogenous myosin light chain kinase. In conclusion, our results suggest that, although Ca2+binding to the troponin-tropomyosin complex is the primary regulator of skeletal muscle contraction, RLC play an important modulatory role in this process.

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Metabolic responses from rest to steady state determine contractile function in ischemic skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.273.2.e233 ◽

1997 ◽

Vol 273 (2) ◽

pp. E233-E238 ◽

Cited By ~ 17

Author(s):

J. A. Timmons ◽

S. M. Poucher ◽

D. Constantin-Teodosiu ◽

I. A. Macdonald ◽

P. L. Greenhaff

Keyword(s):

Skeletal Muscle ◽

Steady State ◽

Muscle Contraction ◽

Metabolic Response ◽

Contractile Function ◽

Pyruvate Dehydrogenase Complex ◽

Force Production ◽

Critical Factor ◽

Control Group ◽

State Force

Skeletal muscle contraction during ischemia, such as that experienced by peripheral vascular disease patients, is characterized by rapid fatigue. Using a canine gracilis model, we tested the hypothesis that a critical factor determining force production during ischemia is the metabolic response during the transition from rest to steady state. Dichloroacetate (DCA) administration before gracilis muscle contraction increased pyruvate dehydrogenase complex activation and resulted in acetylation of 80% of the free carnitine pool to acetylcarnitine. After 1 min of contraction, phosphocreatine (PCr) degradation in the DCA group was approximately 50% lower than in the control group (P < 0.05) during conditions of identical force production. After 6 min of contraction, steady-state force production was approximately 30% higher in the DCA group (P < 0.05), and muscle ATP, PCr, and glycogen degradation and lactate accumulation were lower (P < 0.05 in all cases). It appears, therefore, that an important determinant of contractile function during ischemia is the mechanisms by which ATP regeneration occurs during the period of rest to steady-state transition.

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