Russell D M, Atwood H L, Whittaker J S, Itakura T, Walker P M, Mickle D A, Jeejeebhoy K N
Clin Sci (Lond). 1984 Aug;67(2):185-94. doi: 10.1042/cs0670185.
Previous observations have shown that in human subjects with malnutrition and after prolonged fasting, there are characteristic changes in the force-frequency response, relaxation rate and power of muscle during a 30 s stimulus (fatigue). In order to characterize these findings under carefully controlled conditions, in different types of muscle and to correlate them with changes in muscle structure, composition and biochemical status, we developed an animal model in rats. In this model, nutrient restriction, both after an acute fast and after chronic hypocaloric feeding, resulted in: (a) loss of force during high frequency stimulation but preservation of contraction-relaxation characteristics during low frequency stimulation; (b) slower muscle relaxation rate at high frequency stimulation; (c) increased muscle fatiguability at high frequency stimulation. Measurements of muscle enzymes showed that acute fasting resulted in a reduced content of glycolytic enzymes, but preservation of oxidative enzymes, while chronic hypocaloric dieting resulted in a reduction in both classes of enzyme. There was no significant change in ATP, AMP or energy charge, or in intracellular sodium, potassium and magnesium levels. Creatine phosphate was normal in acutely fasted animals but low in those fed hypocalorically. By contrast, increased intracellular calcium and ADP levels were seen in both fasted and hypocalorically fed animals. These findings suggest that subtle disturbances of intracellular energy states with altered calcium flux may be of importance in the genesis of muscle dysfunction caused by malnutrition.
