Toxin 2 (PhTx2), a neurotoxic fraction from Phoneutria nigriventer spider venom, causes acute morphological changes in mouse skeletal muscle

Phoneutria nigriventer (Labidognatha, Ctenidae) is a spider found in the wa rm regions of South America. Bites by this species cause intense local pain , autonomic dysfunction and paralysis. PhTx2, a neurotoxic fraction of the venom of this species, interferes with the physiology of sodium channel fun ction. The present study describes the morphological changes in mouse phren ic nerve and diaphragm muscle after 15, 30, 45 and 60 min of incubation wit h 1 mu g Of PhTx2/mL. Light and transmission electron microscopy showed tha t PhTx2 caused progressive myonecrosis which involved swelling of the sarco plasmic reticulum, mitochondrial damage, disorganization of the sarcomeres, zones of hypercontracted myofibrils and rupture of the plasma membrane. Th e intramuscular fascicles of the phrenic nerve showed vacuolated myelinated axons and Schwann cells. The neuromuscular junctions had vesicle-depleted nerve terminals with swollen mitochondria. The axolemma was frequently inva ginated and sequestered portions of the axoplasm, or was sometimes interrup ted at the site of the synaptic gutter. The post-synaptic junctional folds were shallow and disperse. These morphological alterations in the muscle an d nerve fibres were similar to those caused by osmotic disturbances and agr ee with the ability of PhTx2 to increase the permeability of sodium channel s. An increase in sodium influx would probably be accompanied by an influx of water and an elevation in the concentration of cytosolic calcium as a re sult of calcium release by the sarcoplasmic reticulum and.;or mitochondria and the entry of extracellular calcium. The morphological effects caused bq PhTx2 were comparable to those seen with Phoneutria nigriventer whole veno m which is known to activate and to delay the inactivation of sodium channe ls. We conclude that PhTx2, is probably the main toxic fraction responsible for such morphological alterations. (C) 2000 Elsevier Science Ltd. All rig hts reserved.