Effect of grayanotoxin on the frog neuromuscular junction.
The effect of alpha-dihydrograyanotoxin II (alpha-H2-GTX II) on the neuromuscular junction of the frog was examined by the intracellular microelectrode technique. alpha-H2-GTX II (6 microM), with a latency of about 20 min, caused a depolarization of both the end-plate and non-end-plate region of the muscle fiber. Concomitantly, alpha-H2-GTX II caused a marked increase in the frequency of m.e.p.p.s, which persisted for 1 hr; thereafter m.e.p.p.s were gradually abolished. In end-plates which had become quiescent after treatment with alpha-H2-GTX II, synaptic vesicles could no longer be recognized histologically, suggesting that alpha-H2-GTX II depleted the store of vesicles. alpha-H2-GTX II did not affect the iontophoretically evoked acetylcholine potential, suggesting that the toxin did not greatly alter the sensitivity of the end-plate membrane to acetylcholine. Removal of Ca++ from the external medium prevented alpha-H2-GTX II from discharging synaptic vesicles. Application of tetrodotoxin or removal of Na+ ions before exposure to alpha-H2-GTX II prevented both the toxin-induced depolarization and increase in m.e.p.p. frequency. It is concluded that the action of GTX on the neuromuscular junction is probably due to an increase in membrane permeability to Na+, resulting in depolarization of both the presynaptic and postsynaptic membranes.
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008854:Microscopy, Electron; D009469:Neuromuscular Junction / Q000502:physiology*; D011898:Ranidae; D012964:Sodium / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology; D014982:Xenopus laevis
D004224:Diterpenes; D014118:Toxins, Biological; C020739:dihydrograyanotoxin II; D013779:Tetrodotoxin; D012964:Sodium; D000109:Acetylcholine; D002118:Calcium