Pharmacological effects and pathological changes induced by the venom of Pseudechis australis in isolated skeletal muscle preparations

Abstract

The venom from the Australian king brown snake Pseudechis australis produced a concentration-dependent and progressive inhibition of directly and indirectly evoked twitches of the mouse hemidiaphragm: 2, 5 and lO μg/ml of venom produced complete blockade of directly evoked twitches after 87 ± 26 min, 66 ± 28 min and 56 ± 13 min, respectively, whereas twitches elicited by indirect stimulation were blocked after 43 ± 4 min, 34 ± 2 min and 21 ± 2 min, respectively. Two, 5 and 10 μg/ml of the venom also progressively inhibited the twitch responses of the chick biventer cervicis muscle evoked by nerve stimulation: the times (min) to 90% blockade of the twitches were 127 ± 12, 41 ± 8 and 26 ± 6, respectively. Light and electron microscopic studies confirmed that the venom caused severe muscle damage and necrosis in the chick and mouse skeletal muscle. The degree of muscle damage was proportional to the concentration of venom used. The muscle degeneration was characterized by disorganized myofibrils, dilatation of the sarcoplasmic reticulum and swollen or brokendown mitochondria. Depletion and a decrease in population of storage vesicles in the neuromuscular junction were also observed. Thus, the inhibition of neuromuscular function by the venom of P. australis was a consequence of the extensive morphological damage to muscle fibres, motor nerve terminals and cytoplasmic organelles which could be attributed to a direct myotoxic action presumably mediated by the enzymatic action of phospholipase A2 present in the venom of P. australis.