Effects of 2 phospholipases a2 from the australian king brown snake (pseudechis-australis) on isolated nerve-muscle preparations

The venom from P. australis is lethal and has phospholipase A activity. Two phospholipases A (Pa-ll and Pa-13) have been isolated; Pa-ll has an LDs0 value of 0.23 ~g/g (i.v.) in mice, whereas Pa-13 was not lethal at 7.4 ~g/g (Nishlda et aI., 1985). In chick biventer cervlcis, Pa-11 (2-20 ~g/ml) reduced responses to indirect stimulation after a prolonged contracture and a transient increase in twitch height. Pa-ll at i0 ~g/ml reduced responses to acetylchollne, carbachol and KCI. At 2 ~g/ml, 50% twitch block was observed after 500 minutes and at 5-20 ~g/ml, complete block was observed after 300 minutes. Pa-13 (at 20 ~g/ml) had no effect on acetylcholine, carbachol and KCl responses, but at 30-40 ~g/ml, these responses were reduced. Neuromuscular block was not observed after 300 minutes at 20-40 ~g/ml. On addition of Pa-13, an immediate, brief contracture occurred. Pa-ll and Pa-13 were tested on mouse hemldlaphragm nerve-muscle preparations stimulated directly and indirectly. The onset of block with Pa-ll was similar at different concentrations, with no lag period. Initially, the blocking rates of the indirect and direct responses were similar but eventually the indirect response was blocked at a faster rate. Only the highest concentration tested (i0 ~g/ml) abolished the direct response. Addition of Pa-ll was followed by muscle contracture and a transient increase in twitch height. Pa-13 (10-20 ~g/ml) caused no increase in indirectly evoked twitches. Contracture occurs at the same time as spontaneous twitching. Neuromuscular block was not observed after 300 minutes.