Alterations of the skeletal muscle contractile apparatus in necrosis induced by myotoxic snake venom phospholipases A2: a mini-review

Skeletal muscle necrosis is a common clinical manifestation of snakebite envenoming. The predominant myotoxic components in snake venoms are catalytically-active phospholipases A(2) (PLA(2)) and PLA(2) homologs devoid of enzymatic activity, which have been used as models to investigate various aspects of muscle degeneration. This review addresses the changes in the contractile apparatus of skeletal muscle induced by these toxins. Myotoxic components initially disrupt the integrity of sarcolemma, generating a calcium influx that causes various degenerative events, including hypercontraction of myofilaments. There is removal of specific sarcomeric proteins, owing to the hydrolytic action of muscle calpains and proteinases from invading inflammatory cells, causing an initial redistribution followed by widespread degradation of myofibrillar material. Experiments using skinned cardiomyocytes and skeletal muscle fibers show that these myotoxins do not directly affect the contractile apparatus, implying that hypercontraction is due to cytosolic calcium increase secondary to sarcolemmal damage. Such drastic hypercontraction may contribute to muscle damage by generating mechanical stress and further sarcolemmal damage.

Automated summary

Snakebite envenoming can lead to skeletal muscle necrosis, and this review focuses on the mechanisms behind it. The toxins in snake venom disrupt the sarcolemma, causing an influx of calcium ions and subsequent degeneration of the muscle fibers. However, experiments suggest that the hypercontraction of muscle fibers is not a direct effect of the toxins, but rather a result of increased cytosolic calcium due to sarcolemmal damage, which may contribute to muscle damage by generating mechanical stress and further sarcolemmal damage.