Effect of "disuse" on mammalian fast-twitch muscle: joint fixation compared with neurally applied tetrodotoxin

The effect of disuse on the functional properties of fast-twitch mammalian muscle is controversial, perhaps because the various disuse models reduce activity to different degrees, and may introduce factors other than reduced activity per se. Our goal was to compare the effects of 14 days of disuse produced by neurally applied tetrodotoxin and joint fixation (knee and ankle) on several morphologic and functional characteristics of the rat gastrocnemius. Joint fixation produced a decrease in muscle wet weight and absolute tetanic tension measured in situ, and a preferential atrophy of slow-twitch fibers. The degree of atrophy was more severe with TTX-disuse and affected all fiber types to the same extent. In further contrast to joint fixation, TTX-disuse caused a preferential loss of myofibrillar protein and a decrease in tetanic tension per unit muscle wet weight. In addition, TTX-disuse resulted in an elevation of twitch:tetanic ratio, a prolonged twitch, and generated a relatively higher proportion of tetanic force at 50 Hz. The normalized maximal rate of tetanic tension development (% Po/ms) was highest in the TTX group. The fatigue index was unaffected by either intervention. The data suggest that complete disuse of mammalian fast-twitch muscle causes atrophy, prolongation of the twitch, and a loss in contractile strength per gram of tissue, and are consistent with qualitative or quantitative changes in the sarcoplasmic reticulum and a decrease in myofibrillar protein concentration with disuse.