Methylmercury-induced depression of neuromuscular transmission in the rat

Effects of bath applied methylmercury on neuromuscular transmission were assessed in the isolated phrenic nerve-hemidiaphragm of adult male rats using conventional microelectrode recording techniques. At concentrations of 20 and 100 microM, methylmercury increased the frequency of miniature end-plate potentials (MEPPs) from control values of 0.3-0.8/sec to 1.5-35/sec. An increase in MEPP frequency occurred after 15-40 min of exposure to 20 microM, and 5-15 min after exposure to 100 microM methylmercury. At a concentration of 4 microM, methylmercury did not increase MEPP frequency, and in fact, slightly decreased it. The increase in MEPP frequency occurred more rapidly and was smaller in magnitude with normal Ca2+ and Mg2+ concentrations (2 mM and 1 mM, respectively) than with low Ca2+ and high Mg2+ (1 mM and 8 mM, respectively) in the bathing solution, although in each case, significant increases in MEPP frequency were observed. The increase in spontaneous neurotransmitter release caused by methylmercury was not reversed by treatment with 1 microM tetrodotoxin. MEPP amplitude was not significantly altered by any concentration of methylmercury tested. End-plate potentials (EPPs) evoked under conditions of diminished quantal content (1 mM Ca2+ and 8 mM Mg2+) were decreased in amplitude, and finally blocked by 20 microM and 100 microM methylmercury, but not by 4 microM methylmercury. EPP block occurred after 30-40 min with 20 microM methylmercury, and after 4-5 min with 100 microM methylmercury. At the time of EPP block, MEPPs of normal size were still observed. The amplitude of end-plate depolarizations produced by iontophoretic application of ACh remained constant during 20-30 min of exposure to 100 microM methylmercury. Quantal content of transmitter release and the immediately available store of neurotransmitter were drastically reduced by higher concentrations of methylmercury, while the probability of release was increased. Resting membrane potentials of muscle fibers were not altered significantly by any concentration of methylmercury tested. The observed effects of methylmercury were not reversible upon washing with drug free solution for one hour. It is suggested that acute methylmercury poisoning irreversibly alters presynaptic function at the mammalian neuromuscular junction.