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

Abstract

Four homologous single chain phospholipases A 2 (Pa-1G, Pa-5, Pa-12C and Pa-15) were tested for neuromuscular effects on chick biventer cervicis and mouse hemidiaphragm nerve-muscle preparations. The four isozymes blocked directly elicited (mouse hemidiaphragm) and indirectly elicited (mouse and chick nerve-muscle preparations) twitch responses in concentrations of 1–30 μg/ml. The order of potency seen in both types of preparations was Pa-1G = Pa-5 > Pa-12C ⪢ Pa-15. All four isozymes caused slow-onset, sustained contractures and reduction of muscle membrane potentials. In the chick preparation, responses to acetycholine, carbachol and KCI were reduced by exposure to the toxins. It is concluded that the toxins act primarily postsynaptically to depress muscle contractility, perhaps by directly damaging muscle fibres. The order of potency agrees with their phospholipase A 2 activity. Pa-1G is unusual because it is an acidic molecule, most toxic phospholipases being basic.