Mechanism of action of myotoxins isolated from snake venoms

Biochemically and pharmacologically, myotoxins isolated from snake venoms can be placed in four main groups: myotoxic phospholipases A, low molecular weight basic toxins, cardiotoxins, and hemorrhagic myotoxins. The myotoxic phospholipases A notexin, taipoxin, crotoxin, and Bothrops asper myotoxin induce muscle necrosis by first affecting the integrity of the plasma membrane, thereby inducing a calcium influx that culminates in cell death. The small basic myotoxin crotamine acts on the voltage-sensitive sodium channels of skeletal muscle sarcolemma, inducing a sodium influx which is responsible for depolarization and contraction of skeletal muscle, as well as for vacuolization of sarcoplasmic reticulum. Cardiotoxins are basic membrane-active polypeptides that disorganize the structure of membranes; the myotoxic activity of cardiotoxins results from their ability to disrupt skeletal muscle sarcolemma. Finally, two hemorrhagic toxins (hemorrhagic toxin b and viriditoxin) are myotoxic; apparently, they secondarily to ischemia which develops in muscular tissue as a consequence of the hemorrhagic action of these toxins.