The Early Expression of Myotoxicity and Localization of the Binding Sites of Notexin in the Soleus Muscle of the Rat

Abstract

Notexin is a major toxic component of the venom of the Australian tiger snake, Notechis scutatus scutatus . It is a peptide of 119 residues with 7 disulphide bridges and a relative molecular mass of 13.6 KDa. Notexin is one of a group of neurotoxic myotoxins that exhibit phospholipase A₂ activity and are homologous with mammalian pancreatic phospholipases (Harris, 1991). The pathological responses of skeletal muscle to notexin and related toxins have been well documented (Harris and Cullen, 1990) but little is known of the precise mechanism of action of the toxins. Based on a great deal of descriptive data, Harris (1984) suggested that the hydrolysis and fragmentation of the the plasma membrane was the primary event, leading to the loss of ionic gradients, influx of Ca²⁺, hypercontraction and degeneration of major muscle fibre proteins. It was conceded, however, that the physical disintegration of the membrane was not a necessary prerequisite for the onset of degeneration, and that the hydrolysis of membrane lipids could lead to a “leaky” membrane without evidence of structural damage.