King Brown Snake Pseudechis Australis Research Articles

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

S. Z. J. Chen, P. Gopalakrishnakone and M. C. E. Gwee. Pharmacological effects and pathological changes induced by the venom of Pseudechis australis in isolated skeletal muscle preparations. Toxicon 32, 303–315, 1994.—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 10 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 broken-down 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 A 2 present in the venom of P. australis.

Pathological and pharmacological effects of the venom of the Australian king brown snake Pseudechis australis on the mouse phrenic nerve-hemidiaphragm: S. Z. J. Chen, P. Gopalakrishnakone1 and M. C. E. Gwee (Venom and Toxin Research Group (Departments of Pharmacology and Anatomy 1), Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore 0511)

Pathological and pharmacological effects of the venom of the Australian king brown snake Pseudechis australis on the mouse phrenic nerve-hemidiaphragm: S. Z. J. Chen, P. Gopalakrishnakone1 and M. C. E. Gwee (Venom and Toxin Research Group (Departments of Pharmacology and Anatomy 1), Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore 0511)

Neuromuscular effects of three phospholipases A 2 from the venom of the Australian king brown snake Pseudechis australis

—Three single chain phospholipases A 2 (Pa-10A, Pa-11 and Pa-13) isolated from Australian king brown snake ( Pseudechis australis) venom were tested for effects on neuromuscular transmission and muscle contractility on chick biventer cervicis and mouse diaphragm preparations. At 1 μg/ml (about 85 nM) and higher, Pa-10A and Pa-11 reduced responses of both preparations to indirect stimulation in a concentration-dependent manner. Responses to direct muscle stimulation were generally reduced more slowly. Pa-11 also decreased membrane potentials of chick biventer muscle fibres and caused damage visible by light microscopy. Pa-13, which is about 50 times less active as a phospholipase A 2, was also less potent in its pharmacological effects: 20 μg Pa-13 per ml were required to reduce responses of either preparation. The phospholipases A 2 also caused a slow contracture. After block of responses to nerve stimulation, responses of the chick preparation to acetylcholine, carbachol and KCl could be obtained, although they were smaller than control and highly variable in different preparations. It is concluded that Pa-10A and Pa-11 produce muscle paralysis by reducing acetylcholine release and by a direct blockade of muscle fibre contractility. Pa-13 has similar, though less pronounced, activities.