title: Effects of methylmercury on perineurial Na+ and Ca(2+)-dependent potentials at neuromuscular junctions of the mouse.
abstract: The ability of acute application of the neurotoxicant methylmercury (MeHg) to disrupt the function of presynaptic Ca2+ and Na+ channels at intact neuromuscular junctions was examined using mouse triangularis sterni motor nerves. In Ba(2+)-containing solutions, potential changes arising from Na+ and Ca2+ channel function could be recorded from the perineurial sheath surrounding motor neurons when K+ channels were blocked by tetraethylammonium chloride and 3,4-diaminopyridine. MeHg (100 microM) reduced both Na(+)- and Ba(2+)-dependent components to block within 3-5 min at apparently equivalent rates. Time to block was approximately 7 min after exposure to 50 microM MeHg. In 2 of 5 preparations exposed to 50 microM MeHg, the Ca2+ channel-mediated component was blocked prior to the Na+ channel-mediated component. In the remaining three preparations, Na(+)- and Ba(2+)-dependent potentials were blocked at similar times. Following block by MeHg, neither perfusing the preparation in MeHg-free solutions nor increasing the intensity and/or duration of stimulus to the intercostal nerves resulted in recovery of Na+ or Ca2+ potentials. In the presence of K+ channel blockers, repetitive firing of nerves in response to a single stimulus was observed in 20-30% of the triangularis preparations; in the two preparations treated with MeHg in which repetitive firing was observed, it decreased prior to block of the stimulus-induced Na+/Ba2+ potentials. These results corroborate the results obtained in isolated synaptosomes and pheochromocytoma cells, and suggest that MeHg decreases motor nerve excitability by disrupting Na+ channel function and may block neurotransmitter release by disrupting Na+ and Ca2+ channel function.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317.
authors.forename: T J
authors.initials: TJ
authors.lastname: Shafer
authors.forename: W D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001464:Barium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D008767:Methylmercury Compounds; D015222:Sodium Channels; D013757:Tetraethylammonium Compounds; D001464:Barium; D015761:4-Aminopyridine; D000077770:Amifampridine