Mode of neuromuscular blocking action of a toxic phospholipase A2 from Pseudocerastes fieldi (Field's horned viper) snake venom.

The effects of a toxic phospholipase A2 (Fr.Cb) isolated from the venom of Pseudocerastes fieldi were studied on the chick biventer cervicis muscle and the mouse phrenic nerve--diaphragm preparations. In the chick muscle, Fr.Cb (10 micrograms/ml) caused complete neuromuscular blockade without producing contracture or affecting the response of the muscle to acetylcholine. In the mouse diaphragm, Fr.Cb blocked the indirectly elicited contraction without affecting that evoked directly. In a low calcium medium (0.5 mM), Fr.Cb produced a triphasic change of the indirectly elicited contractions. The frequency of miniature endplate potentials (m.e.p.p.s) in the mouse diaphragm was first increased 3--4 fold 40 min after toxin (10 micrograms/ml) application, then gradually decreased, while the amplitude of m.e.p.p.s. was not decreased, even after the evoked release of transmitter had failed. Giant m.e.p.p.s were frequently observed. The quantal content first increased and then decreased gradually. The resting membrane potential and the compound phrenic nerve action potential were not significantly affected by the toxin at 10 micrograms/ml after 2 hr of incubation. The motor nerve terminals in the Fr.Cb intoxicated mouse diaphragm showed swelling and vacuolization of both synaptic vesicles and mitochondria. It is concluded that the toxin produces a neuromuscular blockade by acting selectively on the presynaptic site.