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Exposure of relaxed rat extensor digitorum longus (EDL; predominantly fast-twitch) muscle to temperatures in the upper physiological range for mammalian skeletal muscle (43-46 °C) led to reversible alterations of the contractile activation properties. These properties were studied using the mechanically skinned fibre preparation activated in Ca2+-buffered solutions. The maximum Ca2+-activated force (maximum force per cross-sectional area) and the steepness of force-pCa (-log10[Ca2+]) curves as measured by the Hill coefficient (nH) reversibly decreased by factors of 8 and 2.5, respectively, when the EDL muscle was treated at 43 °C for 30 min and 5 and 2.8, respectively, with treatment at 46 °C for 5 min. Treatment at 47 °C for 5 min produced an even more marked depression in maximum specific force, which fully recovered after treatment, and in the Hill coefficient, which did not recover after treatment. After all temperature treatments there was no change in the level of [Ca2+] at which 50 % maximum force was generated. The temperature-induced depression in force production and steepness of the force-pCa curves were shown to be associated with superoxide (O2−) production in muscle (apparent rate of O2− production at room temperature, 0.055 ± 0.008 nmol min−1 (g wet weight)−1; and following treatment to 46 °C for 5 min, 1.8 ± 0.2 nmol min−1 (g wet weight)−1) because 20 mm Tiron, a membrane-permeant O2− scavenger, was able to markedly suppress the net rate of O2− production and prevent any temperature-induced depression of contractile parameters. The temperature-induced depression in force production of the contractile apparatus could be reversed either by allowing the intact muscle to recover for 3-4 h at room temperature or by treatment of the skinned fibre preparation with dithiothreitol (a potent reducing agent) in the relaxing solution. These results demonstrate that mammalian skeletal muscle has the ability to uncouple force production reversibly from the activator Ca2+ as the temperature increases in the upper physiological range through an increase in O2− production.
Skeletal muscle makes up 40 % of the total body mass in eutherian mammals and, when contracted, can generate a large amount of heat (Rall & Woledge, 1990). Therefore, the temperature of working mammalian muscle can be up to 1-2 °C higher than the body core temperature (Baracos et al. 1984). Under certain conditions, such as high-intensity exercise at high ambient temperature and humidity, the body core temperature approaches 43 °C (Furuyama, 1982). Thus the maximal temperature of working muscle in animals undergoing intense exercise is close to the average temperature threshold (45.3 °C) where irreversible temperature-induced damage of muscle cell integrity occurs (Seese et al. 1998).
Interestingly, there is circumstantial evidence to suggest that the contractile apparatus loses its ability to become activated by Ca2+ and develop force at elevated temperatures. This is illustrated by the lack of any sign of contraction of isolated muscle fibres when the temperature was raised gradually to levels where the integrity of the sarcolemma was compromised and Ca2+ would have entered the sarcoplasm from the external environment (Bischof et al. 1995). The reasons for this loss of contractility occurring at high temperatures have not been previously investigated, although it is known that intact limb muscle preparations display poor longevity at temperatures ≥ 37 °C (Segal & Faulkner, 1985; Lännergren & Westerblad, 1987).
In this study, we used single mechanically skinned rat muscle fibre preparations from dissected whole muscle preparations exposed to elevated temperature and examined the effect of temperatures in the upper physiological and immediate supraphysiological range on contractile apparatus function. The results show that increasing the temperature of skeletal muscle to levels in the extreme physiological range markedly reduces the ability of the contractile apparatus to develop maximum Ca2+-activated force through an increase in the production of the superoxide anion. This depression in force-generating capacity is reversible up to 47 °C.