Effects of tetrodotoxin-induced disuse on properties of developing rat gastrocnemius muscle

Our goal was to determine the influence of a complete lack of neuromuscular activity, during a period of rapid muscle growth, on muscle morphology and contractile function. Rats, 21 days old, had one hindlimb paralyzed for a period of 7-9 consecutive days by repetitive implantation of a silastic cuff containing tetrodotoxin (TTX), a specific nerve impulse conduction blocker, around the sciatic nerve. In situ isometric contractile properties of gastrocnemius were measured at 31 days of age, and muscles were subsequently examined histologically. Normal growth during this period resulted in a two- to three-fold increase in muscle weights, mean muscle fiber cross-sectional areas and increases in absolute twitch and tetanic tensions. After inactivity from 21 to 30 days of age, gastrocnemius muscles were smaller, and tetanically weaker, than age-matched controls. The normal cross-sectional area increase of fast-twitch fibers was preferentially affected. Inactive muscles also demonstrated significantly slower twitch responses, had higher twitch:tetanus ratios and relative tensions at 25 Hz than age-matched controls, suggesting a "slower" contractile response. On the other hand, maximum rate of tetanic tension development was elevated. These effects of inactivity appeared to be reversed by resumption of normal activity for 4 days. Neuromuscular inactivity during a relatively short period of rapid muscle growth causes significant muscle morphological and contractile changes, which are most likely reversible.