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J Physiol. 1991 Mar;434:307-22.

Force decline due to fatigue and intracellular acidification in isolated fibres from mouse skeletal muscle.

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  • 1Department of Physiology II, Karolinska Institutet, Stockholm, Sweden.


1. Single, intact muscle fibres from the flexor brevis foot muscle of the mouse have been fatigued at 25 degrees C by 350 ms, 70 Hz stimulation trains, initially delivered every 3.8 s and then at stepwise decreasing intervals until tension was down to about 30% of the original (Po). Rested fibres generated a specific force of 372 +/- 8.4 kPa (mean +/- S.E.M., n = 25). 2. Endurance, defined as time to attain 0.5 Po, varied from 2.5 to 24 min, with the majority of fibres falling in the range 4-8 min, corresponding to 70-160 tetani. In all fibres where it was followed, tension recovery after cessation of stimulation was 90% or better. 3. Tetanic force declined in a characteristic way during fatiguing stimulation: initially tension fell to about 0.85 Po during eight to fourteen tetani (phase 1), then followed a long period of nearly steady tension generation (phase 2) and finally there was a rapid force decline (phase 3). 4. Caffeine (15 or 25 mM) caused a slight potentiation of tetanic force in the rested state (4.7 +/- 0.9%, n = 21) and slowed relaxation. No change in resting tension was seen with caffeine at concentrations up to 25 mM. 5. Caffeine (15-25 mM) caused a rapid and dramatic increase in tetanic force when applied to severely fatigued fibres: force output rose from 29.8 +/- 1.5 to 82.5 +/- 1.2% (n = 13) of Po. During phase 2 force potentiation with caffeine was much smaller. 6. A 10 s pause resulted in a large, transient force increase when imposed during phase 3 but had little effect on force production during phase 2. 7. Intracellular acidosis, induced by superfusion with Tyrode solution gassed with 30% CO2 instead of the normal 5% (extracellular pH 6.5 vs. 7.3), resulted in a fall in tetanic tension to about 0.85 Po (n = 7). This depression could to some extent be counteracted by 15 mM-caffeine, which brought tension back to about 0.90 Po. 8. It is concluded that there are at least two mechanisms for force decline during fatiguing stimulation: one which manifests itself early and is likely to be related to cross-bridge function and another representing deficient Ca2+ handling which becomes prominent at a later stage. For severe fatigue (0.3 Po) the latter mechanism is dominant.

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