Progressive deterioration of muscles in mdx mice induced by overload

1. Extensor digitorum longus muscles of C57 BL/10 and mdx mice were overloaded by removing the synergist tibialis anterior muscle of 9–12-day-old animals. The effect of this operation on the weight, contractile properties and force of the extensor digitorum longus muscle was examined at two different ages, i.e. at 2–3 months (young group) and at 5–8 months (old group). The changes with age in both the control and overloaded muscles of normal and mdx mice are also described. The values obtained from the overloaded muscles were always compared with those for the control, unoperated extensor digitorum longus. 2. In the normal strain of mice the weight of the overloaded extensor digitorum longus muscle in the younger group was increased and it remained higher in the older animals. In the mdx mice the overloaded extensor digitorum longus muscles weighed more in the younger animals but not in the older group of mice. 3. The twitch and tetanic tensions of the overloaded muscles were slightly, but not significantly, increased in the younger group of mdx mice, whereas in the older animals there was a significant decrease in both twitch and tetanic tensions. 4. Thus the overloaded muscles from mdx mice progressively deteriorated with age. In both strains of mice the overloaded muscles become less fatiguable with time.

Resumption of physiological functions in the wood frog (Rana sylvatica) after freezing

We monitored the resumption of physiological functions in frogs that were frozen at -2 to -3 degrees C for 24 h and thawed rapidly (at 23-25 degrees C) or slowly (at 6-8 degrees C). Bodily functions were restored sooner during fast thawing, but this did not enhance the survival of frogs. The first physiological parameter to return was cardiac function, but during the early stages of thawing heart rates were lower than heart rates of unfrozen frogs at comparable body temperatures. Heart rates increased thereafter in conjunction with the rise in frog body temperatures. Spontaneous breathing and hindleg reflexes resumed after cardiac function, but neither response was exhibited by all frogs after the conclusion of the observation periods (3-4 h). Finally, isolated gastrocnemius muscles that had undergone in vitro freezing showed no significant (P greater than 0.05) impairment of twitch and tetanic tensions even as soon as 1 h after the onset of thawing. Body systems thus vary in their rates of recovery after nonlethal freezing episodes. Furthermore, recovery of specific body systems corresponds to essential needs that must be met immediately after thawing, such as reperfusion of body tissues.

Metabolic and contractile responses of rat fast-twitch muscle to 10-Hz stimulation

Contractile and metabolic responses of rat fast-twitch gastrocnemius-plantaris muscles were studied. Acute in situ 10-Hz stimulation (STIM) for two 60-min periods, separated by 60 min of recovery (REC), was used. Muscles were removed at 1, 3, 15, 60, 75, 120, 123, or 180 min for metabolite measurements. Twitch and tetanic tensions were reduced to 36 and 28% of initial during the first 60 min of STIM. During REC, these tensions returned only to 56-58% of initial by 120 min. These contractile responses did not parallel changes in metabolites in mixed muscle. pH was reduced from 7.0 to 6.4 by 1 min, but by 15 min of STIM had returned to resting levels. Free ADP and AMP increased 3- and 15-fold during STIM, then decreased to resting levels by 3 min of REC. The most sensitive indicator of metabolic stress during STIM and REC was the phosphorylation potential, which varied up to 40-fold. After initial phases of depletion, ATP and phosphocreatine levels were partially restored despite ongoing STIM. Approximately 75% of the change in ATP level could be accounted for by IMP. In red gastrocnemius [fast-twitch red (FTR)] muscle, IMP was increased by 3 min of STIM but returned to control values by 60 min. Thus reamination of IMP occurred during contractions of FTR muscle. Metabolic and contractile responses during the second STIM period (120-180 min) were similar to the first. This cycle of metabolic and contractile responses occurs in fast-twitch muscle which, with chronically repeated STIM and REC periods, undergoes large phenotypic changes as a result of use.

Co2+, low Ca2+, and verapamil reduce mechanical activity in rat skeletal muscles

We have studied the effects of Co2+ (5 mM), low-Ca2+ solution [0 added CaCl2, 5 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid, 3 mM MgCl2 Ringer], and verapamil (0.1 mM) on mechanical and electrical properties of rat soleus muscle in vitro at 34 degrees C. Muscle fibers had normal resting potentials in Co2+ and verapamil solutions. Low-Ca2+ solution produces a depolarization of approximately 4 mV. The action potentials are smaller and have a slower time course when exposed to test solutions. Iterative generation of action potentials in the presence of Co2+ and low-Ca2+ solution is not modified. In the presence of Co2+ or low-Ca2+ solution, the mechanical output, twitch and tetanus tensions, and caffeine contracture are reduced significantly. Verapamil produces a decrease in the twitch and tetanic tensions but does not modify the caffeine contracture tension. The effect of verapamil on the twitch becomes more manifest when the muscle is stimulated at 3-5 Hz. We suggest that changes in the action potential characteristics or the inhibition of a Ca2+ current are responsible for the mechanical changes observed in the presence of the drugs.