Differential activation of myofibrils during fatigue in phasic skeletal muscle cells

Abstract

In fatigued muscles the T-system is swollen; thus the action potential may fail to travel along the T-system or the T-tubule terminal cisternae signal may fail to bring about TC Ca2+ release. This would lead to a decrease in the number of myofibrils activated and in force development, but if fatigue is the result of a generalized process, all the myofibrils would be affected equally leading to a lower activation of all of them. We have investigated this possibility in isolated twitch muscle fibres by giving them repetitive tetanic stimulations until fatigue developed. The behaviour of myofibrils was followed with cinemicrophotography. Before fatigue, no lack of shortening of myofibrils could be found. During fatigue groups of myofibrils became wavy. When exposed to caffeine, the wavy myofibrils disappeared and tension similar to the control developed. The tension-caffeine concentration relationship was shifted to the left after development of fatigue. In low Na+ solution fatigue developed faster and after reintroducing normal Ringer, tension recovered substantially. K-contractures were smaller during fatigue. These results indicate that in this type of fatigue, a step in the EC coupling chain of events is involved in its development.

Changes of action potentials and force at lowered [Na+]o in mouse skeletal muscle: implications for fatigue

“…4). Similar effects of lowered [Na ϩ ] o on fatigue have been seen in amphibian muscle (15) and during prolonged continuous tetanic stimulation of mammalian muscle (6,16). Clearly, these results suggest that a small reduction of the Na ϩ gradient can be rate limiting during fatigue.…”

“…Bezanilla et al (4) estimated a 30 mM depletion of Na ϩ in the t tubules during a single 500-ms tetanic contraction at 60 Hz. Other investigators have also suggested that Na ϩ depletion occurs in the t tubules because of diffusion limitations (6,12,15,16 ] o (8); i.e., Na ϩ may have a greater effect in fatigued than in nonfatigued muscle because of the simultaneous decrease in K ϩ gradient (17,19,26) and, possibly, lower t-tubular [Ca 2ϩ ] (8,25). Lowered Na ϩ gradient may also affect the activity of the Na ϩ /Ca 2ϩ (3,25) or Na ϩ /H ϩ exchanger (25), resulting in changes in intracellular [Ca 2ϩ ] and pH, both of which may influence fatigue.…”

Sarcoplasmic reticulum Ca2+release and muscle fatigue

“…This result, confirmed many times (58,62,87,98), pointedly implicates modification of the SR Ca 2ϩ channel during fatiguing protocols.…”

Skeletal Muscle Fatigue: Cellular Mechanisms

“…Some studies in frog single fibers, however, found evidence of T-system AP failure even with intermittent stimulation when tested at short muscle lengths (152,180).…”