title: Toxin 2 (PhTx2), a neurotoxic fraction from Phoneutria nigriventer spider venom, causes acute morphological changes in mouse skeletal muscle.
abstract: Phoneutria nigriventer (Labidognatha, Ctenidae) is a spider found in the warm 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 function. The present study describes the morphological changes in mouse phrenic nerve and diaphragm muscle after 15, 30, 45 and 60 min of incubation with 1 microg of PhTx2/ml. Light and transmission electron microscopy showed that PhTx2 caused progressive myonecrosis which involved swelling of the sarcoplasmic reticulum, mitochondrial damage, disorganization of the sarcomeres, zones of hypercontracted myofibrils and rupture of the plasma membrane. The 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 axolema was frequently invaginated and sequestered portions of the axoplasm, or was sometimes interrupted at the site of the synaptic gutter. The post-synaptic junctional folds were shallow and disperse. These morphological alterations in the muscle and nerve fibres were similar to those caused by osmotic disturbances and agree with the ability of PhTx2 to increase the permeability of sodium channels. 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 result of calcium release by the sarcoplasmic reticulum and/or mitochondria and the entry of extracellular calcium. The morphological effects caused by PhTx2 were comparable to those seen with Phoneutria nigriventer whole venom which is known to activate and to delay the inactivation of sodium channels. We conclude that PhTx2 is probably the main toxic fraction responsible for such morphological alterations.
authors.affiliation: Department of Physiology, Institute of Biology, UNICAMP, Campinas, SP, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Mattiello-Sverzuta
authors.forename: M A
authors.initials: MA
authors.lastname: da Cruz-Höfling
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009469:Neuromuscular Junction / Q000187:drug effects; D009479:Neuropeptides / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D010791:Phrenic Nerve / Q000187:drug effects / Q000648:ultrastructure; D013111:Spider Venoms / Q000633:toxicity*; D013997:Time Factors
chemical_list: D009479:Neuropeptides; D009498:Neurotoxins; D013111:Spider Venoms; C076902:Tx2 neurotoxin