Understanding the in vitro neuromuscular activity of snake venom Lys49 phospholipase A2 homologues

Phospholipases A2 (PLA2s) with a lysine substituting for the highly conserved aspartate 49, Lys49 PLA2 homologues, are important myotoxic components in venoms from snakes of Viperidae family. These proteins induce conspicuous myonecrosis by a catalytically-independent mechanism. Traditionally, the Lys49 PLA2 homologues are classified as non-neurotoxic myotoxins given their inability to cause lethality or paralytic effects when injected in vivo, even at relatively high doses. However, a series of in vitro studies has shown that several Lys49 PLA2 homologues from Bothrops snake venoms induce neuromuscular blocking activity on nerve-muscle preparations in vitro. The interpretation of these findings has created some confusion in the literature, raising the question whether the Lys49 PLA2 homologues present some neurotoxic activity. The present article reviews the in vitro neuromuscular effects of Lys49 PLA2 homologues and discusses their possible mechanisms of action. It was concluded that the neuromuscular blockade induced by Lys49 PLA2 homologues in isolated preparations is mainly a consequence of the general membrane-destabilizing effect of these toxins.