Alteration in skeletal muscle mitochondria of cold-acclimated rats: association with enhanced metabolic response to noradrenaline.

Abstract

This paper reports a search for structural changes in skeletal muscle mitochondria of cold-acclimated rats. Histochemical studies (succinic dehydrogenase) show that there appears to be a higher proportion of red fibers in the semitendinosus muscle of the cold-acclimated rat and that the white region of this muscle contains fibers which resemble intermediate fibers. Electron micrographs show an apparently larger number of small mitochondria in both red and white fibers. Counts of mitochondria isolated from skeletal muscle show that there are more mitochondria per gram of both red and white muscle in the cold-acclimated rat than in the non-acclimated control rat. Each mitochondrion contains less protein and less cytochrome oxidase. Thus the mitochondrial mass per gram of red and white muscle is not altered, as indicated by the unchanged content of mitochondrial protein and of cytochrome oxidase per gram of muscle. Thus there appears to be a repackaging of mitochondrial material into smaller units in the skeletal muscle of the cold-acclimated rat. The alteration is shown to be associated with the adaptive state of the rat. No change occurs in muscle mitochondria of cold-acclimated rats in which the development of the enhanced metabolic response to noradrenaline, a measure of the extent of adaptation, is inhibited by treatment with oxytetracycline. The change in skeletal muscle mitochondria disappears when the enhanced metabolic response to noradrenaline in rats which are already cold-climated is reversed by treating the rats with oxytetracycline while they continue to live in the cold. The change in muscle mitochondria also disappears when the cold-acclimated rat undergoes deacclimation after return to room temperature. The alteration in muscle mitochondria is thus not associated either with shivering or with a high metabolic rate. Skeletal muscle of the cold-acclimated rat is known to be an important site of heat production in the course of nonshivering thermogenesis; that is, it can undergo a considerable increase in metabolic rate in the absence of shivering on exposure of the cold-acclimated rat to cold. The metabolic basis of nonshivering thermogenesis is in an enhanced capacity of the tissues of the cold-acclimated rat, principally skeletal muscle, to respond by an increase in metabolic rate to the large amounts of noradrenaline secreted by the nerve endings of the sympathetic nervous system as a consequence of cold-exposure. The mechanism by which the metabolic response to noradrenaline in the cold-acclimated rat can be enhanced is unknown. The structural alteration observed in the skeletal muscle mitochondria of the cold-acclimated rat may indicate a functional alteration responsible for the enhanced capacity of the muscle to respond to noradrenaline by an increase in metabolic rate.