Fatigability of rat hindlimb muscles after acute irreversible acetylcholinesterase inhibition.

The purpose of this study was to investigate the functional impact of acute irreversible inhibition of acetylcholinesterase (AChE) on the fatigability of medial gastrocnemius and plantaris muscles of Sprague-Dawley rats. After treatment with methanesulfonyl fluoride (a lipid-soluble anticholinesterase), which reduced their AChE activity by >90%, these muscles were subjected to an in situ indirect stimulation protocol, including a series of isolated twitch and tetanic contractions preceding a 3-min fatigue regimen (100-ms trains at 75 Hz applied every 1.5 s). During the first minute of the fatigue regimen, the effects of AChE inhibition were already near maximal, including marked reductions in peak tension and the force-time integral (area), as well as a decrement of compound muscle action potential amplitudes within a stimulus train. Neuromuscular transmission failure was the major contributor of the force decreases in the AChE-inhibited muscles. However, despite this neuromuscular transmission failure, muscles of which all AChE molecular forms were nearly completely inhibited were still able to function, although abnormally, during 3 min of intermittent high-frequency nerve stimulation.

The case for adaptability of the neuromuscular junction to endurance exercise training.

Although the adaptability of the neuromuscular junction (NMJ) has been demonstrated using the models of denervation/reinnervation, electrical stimulation, development, aging, and pathological states, relatively little is known about the effects of increased chronic voluntary use on the morphology and physiological function of the NMJ. A review of findings relating to adaptations in the various pre- and postsynaptic components of the NMJ with exercise training is presented. These findings are discussed as they pertain to NMJ function during exercise. Other physiological modulators of the NMJ, such as trophic factors released by nerve terminals and muscles, and circulating substances are discussed in terms of possible roles they may play in training-induced adaptations.

TTX-induced muscle disuse alters Ca2+ activation characteristics of myofibril ATPase.

1. Previous reports of the effects of disuse induced by tetrodotoxin (TTX) have demonstrated alterations in muscle function suggesting changes in the quality of contractile proteins. 2. We extended these studies to the effects of TTX-induced disuse on the Ca2+ activation characteristics of myofibrillar ATPase of the rat gastrocnemius. 3. Atrophic responses were as previously reported (St-Pierre, D.M.M. and Gardiner P.F. (1985) Effect of disuse on mammalian fast-twitch muscle: joint fixation compared with neurally applied tetrodotoxin. Exp. Neurol. 90, 635-651; St-Pierre, D.M.M. et al. (1987). Recovery of muscle from tetrodotoxin-induced disuse and the influence of daily exercise; 1. Contractile properties. Exp. Neurol. 98, 472-488.) with a significant decrease in left gastrocnemius weight compared to control (C) (1.25 +/- 0.06 for C vs 0.72 +/- 0.04 for TTX, X +/- SEM, P less than or equal to 0.01). 4. Myofibrillar protein yield (mg/g wet weight) was also depressed (92.8 +/- 4.5 for C vs 70.3 +/- 3.7 for TTX; P less than or equal to 0.01). 5. Maximum ATPase of myofibrils (nmol Pi/mg/min) was decreased (441 +/- 28 for C vs 181 +/- 30 for TTX, P less than or equal to 0.01). 6. Furthermore, the Hill n which reflects the cooperative aspects of Ca2+ activation of the myofibrillar ATPase was depressed (1.58 +/- 0.07 for C vs 1.29 +/- 0.09 for TTX; P less than or equal to 0.01). 7. The results suggest that muscle perturbations resulting from disuse are partially related to changes in the myofibril.