Limited oxygen diffusion accelerates fatigue development in mouse skeletal muscle

Abstract

Isolated whole skeletal muscles fatigue more rapidly than isolated single muscle fibres. We have now employed this difference to study mechanisms of skeletal muscle fatigue. Isolated whole soleus and extensor digitorum longus (EDL) muscles were fatigued by repeated tetanic stimulation while measuring force production. Neither application of 10 mM lactic acid nor increasing the [K + ] of the bath solution from 5 to 10 mM had any significant effect on the rate of force decline during fatigue induced by repeated brief tetani. Soleus muscles fatigued slightly faster during continuous tetanic stimulation in 10 mM [K + ]. Inhibition of mitochondrial respiration with cyanide resulted in a faster fatigue development in both soleus and EDL muscles. Single soleus muscle fibres were fatigued by repeated tetani while measuring force and myoplasmic free [Ca 2+ ] ([Ca 2+ ] i ). Under control conditions, the single fibres were substantially more fatigue resistant than the whole soleus muscles; tetanic force at the end of a series of 100 tetani was reduced by about 10% and 50%, respectively. However, in the presence of cyanide, fatigue developed at a similar rate in whole muscles and single fibres, and tetanic force at the end of fatiguing stimulation was reduced by ∼80%. The force decrease in the presence of cyanide was associated with a ∼50% decrease in tetanic [Ca 2+ ] i , compared with an increase of ∼20% without cyanide. In conclusion, lactic acid or [K + ] has little impact on fatigue induced by repeated tetani, whereas hypoxia speeds up fatigue development and this is mainly due to an impaired Ca 2+release from the sarcoplasmic reticulum.

Intracellular calcium accumulation following eccentric contractions in rat skeletal muscle in vivo: role of stretch-activated channels

“…Collectively, these results indicate that survivability of muscle tissue depends strongly on the maintenance of resting blood flow. Indeed, under such in vitro conditions, whole muscle tissue may be more damaged than single-muscle fibers (57). In contrast, in the present investigation, there were no significant changes in resting muscle [Ca 2ϩ ] i under the circulation-intact in vivo conditions.…”

Lack of myostatin results in excessive muscle growth but impaired force generation

“…It has been reported that blockade of mitochondrial respiration in skeletal muscle resulted in decreased tetanic force generation (25,26), and in patients with mitochondrial depletion syndrome, muscle weakness is one leading clinical feature (26,27). Thus, the low specific force in hypertrophic muscle due to lack of myostatin, may be attributable to the associated mitochondrial depletion.…”

Skeletal Muscle Fatigue: Cellular Mechanisms

“…The combination of these issues makes analysis of mechanisms of fatigue in isolated whole muscles problematic. The relative contribution of extracellular accumulation of K ϩ or lactic acid or hypoxia was recently studied in isolated mouse muscle fatigued by repeated tetani, and under these experimental conditions, hypoxia was the most important factor (493).…”