Depression of neuromuscular transmission in methylmercury-poisoned rats: a glass microelectrode and single fiber electromyography study
Corresponding Author
S. Takenaga
Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima
Satoshi Takenaga, Third Department of Internal Medicine, Kagoshima University School of Medicine, 8-35-1, Sakuragaoka, Kagoshima 890, JapanSearch for more papers by this authorK. Arimura
Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima
Search for more papers by this authorK. Miyamoto
National Institute for Minamata Disease, Kumamoto, Japan
Search for more papers by this authorJ. Wakamiya
National Institute for Minamata Disease, Kumamoto, Japan
Search for more papers by this authorM. Osame
Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima
Search for more papers by this authorCorresponding Author
S. Takenaga
Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima
Satoshi Takenaga, Third Department of Internal Medicine, Kagoshima University School of Medicine, 8-35-1, Sakuragaoka, Kagoshima 890, JapanSearch for more papers by this authorK. Arimura
Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima
Search for more papers by this authorK. Miyamoto
National Institute for Minamata Disease, Kumamoto, Japan
Search for more papers by this authorJ. Wakamiya
National Institute for Minamata Disease, Kumamoto, Japan
Search for more papers by this authorM. Osame
Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima
Search for more papers by this authorAbstract
Changes in neuromuscular transmission were examined in methylmercury (MeHg)-poisoned rats, given a total oral dose of 60 mg CH3HgCl at 5 mg/kg/day. A microelectrode study was done on the 21st day. The mean quantal content and mean values of the immediately available pool of ACh in the MeHg-poisoned rats were reduced as compared to those in the control rats, but the mean values for the release probability of ACh did not differ significantly. Stimulation single fiber electromyography (SFEMG) was done on the biceps femoris muscle at 1,5, 10 and 20 Hz on the 28th day. Both a significant and consistent increase in jitter were found at increasing stimulation rates in the MeHg-poisoned rats. The SFEMG findings suggest presynaptic involvement due to accelerated depletion of ACh. We confirmed that neuromuscular transmission is depressed in MeHg-poisoned rats in vivo and in vitro.
References
- 1 Arimura K. Pathomechanism of decremental response in amyotrophic lateral sclerosis. Clin Electroencephalogr 1995: 9: 567–70.
- 2 Arimura K, Murai Y, Rosales RL, Izumo S. Spinal roots of rats poisoned with methylmercury: physiology and pathology. Muscle Nerve 1988: 11: 762–8.
- 3 Atchison WD, Narahashi T. Methylmercury-induced depression of neuromuscular transmission in the rat. Neurotoxicology 1982: 3: 37–50.
- 4 Bakir F, Damluji SF, Amin Zaki L ET AL. Methylmercury poisoning in Iraq. Science 1973: 181: 230–41.
- 5 Bennett MR, Florin T. A statistical analysis of the release of acetylcholine at newly formed synapses in striated muscle. J Physiol (Lond) 1974: 238: 93–107.
- 6 Blasi J, Chapman E, Link E et al. Botulinum neurotoxin A selectively cleaves the synapse protein SNAP-25. Nature 1993: 265: 160–3.
- 7 Hunter D, Bomford RR, Russell DS. Poisoning by methylmercury compounds. Quart J Med 1940: 33: 193–241.
- 8 Lambert EH, Elmquist D. Quantal components of end-plate potentials in the myasthenic syndrome. Ann NY Acad Sci 1971: 183: 183–99.
- 9 Levesque PC, Atchison WD. Interactions of mitochondrial inhibitors with methylmercury on spontaneous quantal release of acetylcholine. Toxicol Appl Pharmacol 1987: 87: 315–24.
- 10 Levesque PC, Hare MF, Atchison WD. Inhibition of mitochondrial Ca2+ release diminishes the effectiveness of methyl mercury to release acetylcholine from synapto-somes. Toxicol Appl Pharmacol 1992: 115: 11–20.
- 11 Magleby KL. Neuromuscular Transmission. In: AG Engel et al., eds. Myology. New York : McGraw-Hill, 1994: 442–63.
- 12 Martin AR. A further study of the statistical component of the end-plate potential. J Physiol Lond 1955: 130: 114–22.
- 13 Maselli RA, Cashman NR, Wollman RL, Salazar-Grueso EF, Roos R. Neuromuscular transmission as a function of motor unit size in patients with prior poliomyelitis. Muscle Nerve 1992: 15: 648–55.
- 14 Maselli RA, Woolmann RL, Leung C, Salazar-Grueso EF, Roos RP Neurophysiological and morphological abnormalities at the neuromuscular junction in patients with post-poliomyelitis syndrome. Neurology (Suppl. 13) 1992: 42: 231.
- 15 Maselli RA, Wollman RL, Leung C et al. Neuromuscular transmission in amyotrophic lateral sclerosis. Muscle Nerve 1993: 16: 1193–203.
- 16 McLachlan EM. The statistics of transmitter release at chemical synapses. In: R Porter, ed. International Review of Physiology Neurophysiology III. Baltimore : University Park Press, 1978, vol 17: 83–115.
- 17 Miyamoto MD. Binomial analysis of quantal transmitter release at glycerol-treated frog neuromuscular junctions. J Physiol Lond 1975: 250: 121–42.
- 18
Rosales RL,
Arimura K,
Takenaga S,
Osame M.
Extra-fusal and intrafusal muscle effects in experimental botuli-num toxin-A injection.
Muscle Nerve
1996: 19: 488–96.
10.1002/(SICI)1097-4598(199604)19:4<488::AID-MUS9>3.0.CO;2-8 CAS PubMed Web of Science® Google Scholar
- 19 Rustam H, Von Burg R, Amin Zaki L, El Hassani S. Evidence for a neuromuscular disorder in methylmercury poisoning. Arch Environ Health 1975: 30: 190–5.
- 20 Schiller HH, Stalberg E. Human botulism studied with single-fiber electromyography. Arch Neurol 1978: 35: 346–9.
- 21 Shafer TJ, Atchison WD. Methylmercury blocks N- and L-type Ca++ channels in nerve growth factor-differentiated pheochromocytoma (PC12) cells. J Pharmacol Exp Ther 1991: 258: 149–57.
- 22 Shafer TJ, Atchison WD. Effects of methylmercury on perineurial Na+- and Ca(2+)-dependent potentials at neuromuscular junctions of the mouse. Brain Res 1992: 595: 215–19.
- 23 Shiraki H. Neuropathological aspects of organic mercury intoxication, including Minamata disease. In: PJ Vinken et al., eds. Handbook of Clinical Neurology. Intoxications of The Nervous System Part I. New York : Elsevier, 1979, vol 36: 83–145.
- 24 Somjen GG, Herman SP, Klein R. Electrophysiology of methylmercury poisoning. J Pharmacol Exp Ther 1973: 186: 579–92.
- 25 Stalberg E, Hilton-Brown P, Rydin E. Capacity of the motor neuron to alter its peripheral field. In: MR Dimitruevic et al., eds. Recent Achievements in Restorative Neurology 2: Progressive Neuromuscular Diseases. Basel : Karger, 1986: 237–53.
- 26 Stalberg E, Tronteu JV. Single Fiber Electromyography: Studies in healthy and diseased muscle, 2nd edition. New York : Raven Press, 1994: 130–219.
- 27 Takeuchi T, Eto K. Pathology and pathogenesis of Minamata disease. In: T Tsubaki et al., eds. Methylmercury Poisoning in Minamata and Niigata, Japan. Amsterdam : Kodansha and Elsevier, 1977: 103–141.
- 28
Takeuchi T,
Morikawa N,
Matsumoto H,
Shiraishi Y.
A pathological study of Minamata disease in Japan.
Acta Neuropath
1962: 2: 40–57.
10.1007/BF00685743 Google Scholar
- 29 Traxinger DL, Atchisib WD. Reversal of methylmercury-induced block of nerve-evoked release of acetylcholine at the neuromuscular junction. Toxicol Appl Pharmacol 1987: 90: 23–33.
- 30 Trojan DA, Gendron D, Cashman NR. Stimulation frequency-dependent neuromuscular junction transmission defects in patients with prior poliomyelitis. J Neurol Sci 1993: 118: 150–7.
- 31 Trontelj JV, Stalberg E. Single motor end-plates in myasthenia gravis and LEMS at different firing rates. Muscle Nerve 1991: 14: 226–32.
- 32 Tsujihata M, Hazama R, Yoshimura T, Satoh A, Mori M, Nagataki S. The motor end-plate fine structure and ultrastructural localization of acetylcholine receptors in amyotrophic lateral sclerosis. Muscle Nerve 1984: 7: 243–9.
- 33 Verschuuren JJ, Spaans F, De Baets MH. Single-fiber electromyography in experimental autoimmune myasthenia gravis. Muscle Nerve 1990. 13: 485–92.
- 34 Wiechers DO. New concepts of the reinnervated motor unit revealed by vaccine-associated poliomyelitis. Muscle Nerve 1988: 11: 356–64.
- 35 Yip RK, Riley DA. Effects of methylmercury on the motor and sensory innervation of the rat extensor digitorum longus muscle. Environ Res 1987: 43: 85–96.
