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.