Neuromuscular effects of a toxic phospholipase-a2 isolated from venom of the solomon-island sea-snake laticauda-colubrina

A phospholipase A, (Lc PLA-BII) has an LDs0 value of 48 ng/g (i.v.) in mice. A homologous protein (Lc PLH) has no phospholipase or lethal activities. The neuromuscular activities of the Lc PLA-BII and Lc PLH were tested on chick biventer cervicls and mouse hemidiaphragm preparations. At 5-20 ~g/ml, Lc PLA-EII depressed responses of the biventer cervlcis preparation to nerve stimulation and also acetylchollne and carbachol responses, indicating a post-junctional effect. This was not observed at lower concentrations which still abolished responses to indirect stimulation. Therefore, at these concentrations neuromuscular block was a prejunctional phenomenon. This anomaly may be due to contamination of the phospholipase component by a postjunctlonal neurotoxin. There was little direct effect on muscle contractillty. Immediately after addition of the toxin, a transient increase in twitch height was observed, and onset of neuromuscular block follOWed without a lag period. No contracture was observed. Lc PLA-BII reduced responses of mouse diaphragm preparations to indirect stimulation after a lag period. Preceding the lag period a transient increase in twitch height was observed at all concentrations tested (0.1-5 ~g/ml). Interestingly, the lag period at each of theconcentrations tested was of similar duration.The homologue Lc PLH (5-20 ~g/ml) reduced the responses of the blventer cervicls preparation to indirect stimulation, abolished acetylcholine and carbachol responses but had little effect on responses to KCI. At 20~g/ml, twitches were reduced by 50% after i00 minutes. No lag period was observed. When tested on indirectly stimulated mouse hemidiaphragms, little effect was observed after 5 hours at 5-10 ~g/ml.