Reversible changes in Ca(2+)-activation properties of rat skeletal muscle exposed to elevated physiological...

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 degrees C) led to reversible alterations of the contractile activation properties. These properties were studied using the mechanically skinned fibre preparation activated in Ca(2+)-buffered solutions. The maximum Ca(2+)-activated force (maximum force per cross-sectional area) and the steepness of force-pCa (-log(10)[Ca(2+)]) curves as measured by the Hill coefficient (n(H)) reversibly decreased by factors of 8 and 2.5, respectively, when the EDL muscle was treated at 43 degrees C for 30 min and 5 and 2.8, respectively, with treatment at 46 degrees C for 5 min. Treatment at 47 degrees 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 [Ca(2+)] 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 (O(2)(-)) production in muscle (apparent rate of O(2)(-) production at room temperature, 0.055 +/- 0.008 nmol min(-1) (g wet weight)(-1); and following treatment to 46 degrees C for 5 min, 1.8 +/- 0.2 nmol min(-1) (g wet weight)(-1)) because 20 mM Tiron, a membrane-permeant O(2)(-) scavenger, was able to markedly suppress the net rate of O(2)(-) 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 Ca(2+) as the temperature increases in the upper physiological range through an increase in O(2)(-) production.