Skeletal Muscle Toxicology

The skeletal musculature is necessary for normal motor functions such as walking or breathing. It accounts for between 35 and 45% of total body weight in humans and is the most energetically demanding tissue in the body. Skeletal muscle is a unique tissue with intricate organizational arrangement, requiring precise regulation of intracellular ions and cooperation by a multitude of cellular proteins. As a result, it also has susceptibilities to a diverse array of toxic insults. Derangements of skeletal muscle function can cause loss of movement, multiorgan involvement and even organismal demise. In addition to direct effects on skeletal muscle, this tissue can also be responsible for damage to distant tissues and organs by release of large intracellular proteins into the vasculature. As a specific topic, skeletal muscle toxicology has been largely absent from the majority of textbooks. However, it represents an important and specific target of a variety of natural and synthetic toxicants. Here we present an overview of skeletal muscle physiology, including tissue architecture, energetic substrate preferences, and function. Laboratory methods and diagnostic observations to be used for investigating skeletal muscle injury in a research and clinical setting are also discussed. Finally, we provide an in-depth outline of skeletal muscle toxicants arranged according to their proposed mechanism of action. Keywords: skeletal muscle; toxicology; rhabdomyolysis; myopathy; sarcoplasmic; myotube; hyperthermia; thermogenesis; myotoxic