Abstract
Fatigue in muscles that shorten might have other causes than fatigue during isometric contractions, since both cross-bridge cycling and energy demand are different in the two exercise modes. While isometric contractions are extensively studied, the causes of fatigue in shortening contractions are poorly mapped. Here, we investigate fatigue mechanisms during shortening contractions in slow twitch skeletal muscle in near physiological conditions. Fatigue was induced in rat soleus muscles with maintained blood supply by in situ shortening contractions at 37°C. Muscles were stimulated repeatedly (1 s on/off at 30 Hz) for 15 min against a constant load, allowing the muscle to shorten and perform work. Fatigue and subsequent recovery was examined at 20 s, 100 s and 15 min exercise. The effects of prior exercise were investigated in a second exercise bout. Fatigue developed in three distinct phases. During the first 20 s the regulatory protein Myosin Light Chain-2 (slow isoform, MLC-2s) was rapidly dephosphorylated in parallel with reduced rate of force development and reduced shortening. In the second phase there was degradation of high-energy phosphates and accumulation of lactate, and these changes were related to slowing of muscle relengthening and relaxation, culminating at 100 s exercise. Slowing of relaxation was also associated with increased leak of calcium from the SR. During the third phase of exercise there was restoration of high-energy phosphates and elimination of lactate, and the slowing of relaxation disappeared, whereas dephosphorylation of MLC-2s and reduced shortening prevailed. Prior exercise improved relaxation parameters in a subsequent exercise bout, and we propose that this effect is a result of less accumulation of lactate due to more rapid onset of oxidative metabolism. The correlation between dephosphorylation of MLC-2s and reduced shortening was confirmed in various experimental settings, and we suggest MLC-2s as an important regulator of muscle shortening.
Highlights
Skeletal muscle contraction is a complex process, and the precise mechanisms that mediate fatigue have yet to be fully understood
A few studies have investigated the effect of contraction mode on fatigue development, and they reported significantly larger fatigue development during shortening as compared to isometric contractions [3,4,5,6], suggesting that fatigue development is dependent on the type of muscle contraction
Ethics Statement All experiments and animals were handled in strict accordance to the Norwegian Animal Welfare Act, and protocols were approved by the Norwegian Animal Research Authority
Summary
Skeletal muscle contraction is a complex process, and the precise mechanisms that mediate fatigue have yet to be fully understood (for review see [1]). In the present study we used an in situ model of dynamic muscle activity [2] which provides an experimental setting with maintained blood supply, and allows an extended investigation of fatigue mechanisms during shortening muscle contractions. A few studies have investigated the effect of contraction mode on fatigue development, and they reported significantly larger fatigue development during shortening (isotonic, dynamic) as compared to isometric contractions [3,4,5,6], suggesting that fatigue development is dependent on the type of muscle contraction. Only 5% of cycle time is spent in the high force generating configuration [8], and the rate limiting step might be different. Using force as the only fatigue variable may underestimate the functional impairment of the fatigued muscle during shortening contractions [2,5], and additional parameters like extent of muscle shortening and velocities of contraction and relengthening could provide a more comprehensive fatigue analysis
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