Skip to main content
SpringerLink
Log in

Role of Neuronal Ion Channels in Mercury Intoxication

  • Chapter
Advances in Mercury Toxicology

Part of the book series: Rochester Series on Environmental Toxicity ((RSET))

  • 255 Accesses

Abstract

Mercury compounds exert multiple actions on the nervous system. At skeletal neuromuscular junctions, mercury increases spontaneous release of acetylcholine from nerve terminals and suppresses the nerve-evoked synchronized release of acetylcholine. Voltage-activated sodium and potassium channels of neuronal membranes are suppressed by mercury causing conduction block. Our recent patch clamp study with the rat dorsal root ganglion neurons has unveiled a highly potent and efficacious action of mercuric chloride in augmenting the GABA-activated chloride channel current, a prominent effect being observed at 1 μM. Mercuric chloride also induced a slow inward current by itself, which is likely to account for an increase in leakage current, resting membrane conductance, and membrane depolarization. It was concluded that the stimulation of GABA-induced chloride current plays an important role in mercury intoxication.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abdallah, E. A. M. and Shamoo, A. E., 1984. Protective effect of dimercaptosuccinic acid on methylmercury and mercuric chloride inhibition of rat brain muscarinic acetylcholine receptors. Pesticide Biochem. Physiol. 21:385–393.

    Article  CAS  Google Scholar 

  • Abd-Elfattah, A. S. A., and Shamoo, A. E., 1981, Regeneration of a functionally active rat brain muscarinic receptor by d-penicillamine after inhibition with methylmercury and mercuric chloride. Evidence for essential sulfhydryl groups in muscarinic receptor binding sites, Mol. Pharmacol., 20:492–497.

    PubMed  CAS  Google Scholar 

  • Arakawa, O., Nakahiro, M., and Narahashi, T., 1991, Mercury modulation of GABA-activated chloride channels and non-specific cation channels in rat dorsal root ganglion neurons, Brain Res. 551:58–63.

    Article  PubMed  CAS  Google Scholar 

  • Atchison, W. D., 1986, Extracellular calcium-dependent and-independent effects of methylmercury on spontaneous and potassium-evoked release of acetylcholine at the neuromuscular junction, J. Pharmacol. Exp. Ther., 237:672–680.

    PubMed  CAS  Google Scholar 

  • Atchison, W.D., 1987, Effects of activation of sodium and calcium entry on spontaneous release of acetylcholine induced by methylmercury, J. Pharmacol. Exp. Then, 241:131–139.

    CAS  Google Scholar 

  • Atchison, W. D., and Narahashi, T., 1982, Methylmercury-induced depression of neuromuscular transmission in the rat, NeuroToxicoloty, 3:37–50.

    CAS  Google Scholar 

  • Bakir, R., Damluji, S. F., Amin-Zaki, L., Murtadha, M., Khalidi, A., Al-Rawi, N. Y., Tikriti, S., Dhahir, H. I., Clarkson, T. W., Smith, J. C., and Doherty, R. A., 1973, Methylmercury poisoning in Iraq, Science, 181:230–240.

    Article  PubMed  CAS  Google Scholar 

  • Barker, J. L., and Ransom, B. R., 1978, Pentobarbitone pharmacology of mammalian central neurones grown in tissue culture, J. Physiol. (London), 280:355–372.

    CAS  Google Scholar 

  • Barrett, J., Botz, D., and Chang, D.B., 1974, Block of neuromuscular transmission by methylmercury, in: “Behavioral Toxicology, Early Detection of Occupational Hazards,” C. Xintaras, B. L. Johnson and I. de Groot, eds., Vol. 5, 277–287, U.S. Dept. of Health, Education and Welfare, Washington.

    Google Scholar 

  • Berlin, M., Carlson, J., and Norseth, T., 1975, Dose-dependence of methylmercury metabolism, Arch. Environ. Health, 30:307–317.

    Article  PubMed  CAS  Google Scholar 

  • Bondy, S. C., and Agrawal, A. K., 1980, The inhibition of cerebral high affinity receptor sites by lead and mercury compounds, Arch. Toxicol., 46:249–256.

    Article  PubMed  CAS  Google Scholar 

  • Bormann, J., and Clapham, D. E., 1985, γ-Aminobutyric acid receptor channels in adrenal chromaffin cells: A patch-clamps study, Proc. Natl. Acad. Sci. USA, 82:2168–2172.

    Article  PubMed  CAS  Google Scholar 

  • Brown, D. A., and Constanti, A., 1978, Interaction of pentobarbitone and γ-aminobutyric acid on mammalian sympathetic ganglion cells, Brit. J. Pharmacol., 63:217–224.

    Article  CAS  Google Scholar 

  • Cavanaugh, J. B., and Chen, F. C. K., 1971, The effects of methyl-mercury-dicyandiamide on the peripheral nerves and spinal cord of rats, Acta Neuropathol., 19:208–215.

    Article  Google Scholar 

  • Chan, C. Y., and Farb, D. H. 1985, Modulation of neurotransmitter action: Control of the γ-aminobutyric acid response through the benzodiazepine receptor, J. Neuroscience, 5:2365–2373.

    CAS  Google Scholar 

  • Chang, L. W., 1977, Neurotoxic effects of mercury—a review, Environ. Res., 14:329–373.

    Article  PubMed  CAS  Google Scholar 

  • Chang, L. W., 1980, Mercury in: “Environmental and Clinical Neurotoxicology,” P.S. Spencer and H. H. Schaumburg, eds., 508–526, The Williams and Wilkins, Baltimore.

    Google Scholar 

  • Chang, L. W., and Hartmann, H. A., 1972, Ultrastructural studies of the nervous system after mercury intoxication. II. Pathological changes in the nerve fibers, Acta Neuropathol., 20:316–331.

    Article  PubMed  CAS  Google Scholar 

  • Choi, D. W., Farb, D. H., and Fischbach, G. D., 1981, Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture, J. Neurophysiol., 45:621–631.

    PubMed  CAS  Google Scholar 

  • Cooper, G. P., and Manalis, R. S. 1983, Influence of heavy metals on synaptic transmission, NeuroToxicology, 4:69–84.

    PubMed  CAS  Google Scholar 

  • Cooper, G. P., Suszkiw, J. B., and Manalis, R. S., 1984, Heavy metals: Effects on synaptic transmission, NeuroToxicology, 5:247–266.

    PubMed  CAS  Google Scholar 

  • Eldefrawi, M. E., Monsour, N. A., and Eldefrawi, A. T., 1977, Interactions of acetylcholine receptors with organic mercury compounds, in: “Membrane Toxicity,” M.W. Miller and A.E. Shamoo, eds., 449–463, Plenum, New York.

    Chapter  Google Scholar 

  • Fehling, C., Abdulla, M., Brun, A., Dictor, M., Schütz, A., and Skerfving, S., 1975, Methylmercury poisoning in the rat: A combined neurological, chemical and histopathological study, Toxicol. Appl. Pharmacol., 33:27–37.

    Article  PubMed  CAS  Google Scholar 

  • Hamill, O. P., Marty, A., Neher, E., Sakmann, B., and Sigworth, F. J., 1981, Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches, Pflügers Arch., 391:85–100.

    Article  PubMed  CAS  Google Scholar 

  • Herman, S. P., Klein, R., Talley, F. A., and Krigman, M. R., 1973, An ultrastructural study of methylmercury-induced primary sensory neuropathy in the rat, Lab. Invest., 28:104–118.

    PubMed  CAS  Google Scholar 

  • Hift, H., and Schultz, R., 1976, Methylmercury induced injury of single barnacle muscle fibers, Environmental Res., 11:367–385.

    Article  CAS  Google Scholar 

  • Hughes, W. L., 1957, A physicochemical rationale for the biological activity of mercury and its compounds, Ann. New York Acad. Sci., 65:454–460.

    Article  CAS  Google Scholar 

  • Hunter, D., Bomford, R., and Russell, D. S., 1940, Poisoning by methylmercury compounds, Quart. J. Med., 9:193–241.

    CAS  Google Scholar 

  • Jacobs, J. M., Carmichael, N., and Cavanaugh, J. B., 1975, Ultrastructural changes in the dorsal root and trigeminal ganglia of rats poisoned with methylmercury, Neuropathol. Appl. Neurobiol., 1:1–9.

    Article  CAS  Google Scholar 

  • Juang, M. S., 1976, An electrophysiological study of the action of methylmercuric chloride and mercuric chloride on the sciatic nerve-sartorius muscle preparation of the frog, Toxicol. Appl. Pharmacol., 37:339–348.

    Article  PubMed  CAS  Google Scholar 

  • Juang, M. S., and Yonemura, K., 1975, Increased spontaneous transmitter release from presynaptic nerve terminal by methylmercuric chloride, Nature (London), 256:211–213.

    Article  CAS  Google Scholar 

  • Kato, E., Anwyl, R., Quandt, F. N., and Narahashi, T., 1983, Acetylcholine-induced electrical responses in neuroblastoma cells, Neuroscience, 8:643–651.

    Article  PubMed  CAS  Google Scholar 

  • Le Quesne, P. M., Damaluji, S. F., and Rustam, H., 1974, Electrophysiological studies of peripheral nerves in patients with organic mercury poisoning, J. Neurol. Neurosurg. Psychol., 37:333–338.

    Article  Google Scholar 

  • Levesque, P. C., and Atchison, W. D., 1987, Interactions of mitochondrial inhibitors with methyl mercury on spontaneous quantal release of acetycholine, Toxicol. Appl. Pharmacol., 87:315–324.

    Article  PubMed  CAS  Google Scholar 

  • Levesque, P. C., and Atchison, W. D., 1988, Effect of alteration of nerve terminal Ca2+ regulation on increased spontaneous quantal release of acetylcholine by methylmercury, Toxicol. Appl. Pharmacol., 94:55–65.

    Article  PubMed  CAS  Google Scholar 

  • Macdonald, R. L., and Barker, J. L., 1979, Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: A common mode of anticonvulsant action, Brain Res., 167:323–336.

    Article  PubMed  CAS  Google Scholar 

  • Manalis, R. S., and Cooper, G. P., 1975, Evoked transmitter release increased by inorganic mercury at frog neuromuscular junction, Nature (London), 257:690–691.

    Article  CAS  Google Scholar 

  • Marco, L. A., Isaacson, L., and Torri, J. C., 1979, Effects of mercuric chloride on the resting membrane potentials of blue crab (Callinectes sapidus) muscle fibers, Toxicology, 12:41–46.

    Article  PubMed  CAS  Google Scholar 

  • Misumi, J., 1979, Electrophysiological studies in vivo on peripheral nerve function and their application to peripheral neuropathy produced by organic mercury in rats. III. Effects of methylmercuric chloride on compound action potentials in the sciatic and tail nerve in rats, Kumamoto Med. J., 32:15–22.

    CAS  Google Scholar 

  • Miyakawa, T., Deshimaru, M., Sumiyoshi, S., Teraoka, A., Udo, N., Hattori, E., and Tatetsu, S., 1970, Experimental organic mercury poisoning—Pathological changes in peripheral nerves, Acta Neuropathol., 15:45–55.

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto, M. D., 1983, Hg2+ causes neurotoxicity at an intracellular site following entry through Na and Ca channels, Brain Res., 267:375–379.

    Article  PubMed  CAS  Google Scholar 

  • Nakahiro, M., Yeh, J. Z., Brunner, E., and Narahashi, T., 1989, General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons, Faseb J., 3:1850–1854.

    PubMed  CAS  Google Scholar 

  • Nakahiro, M., Arakwara, O., and Narahashi, T., 1991. Modulation of GABA receptor-channel complex by alcohols. J. Pharmacol. Exp. Ther., in press.

    Google Scholar 

  • Neher, E., and Sakmann, B., 1976, Single-channel currents recorded from membrane of denervated frog muscle fibres, Nature (London), 260:779–802.

    Article  Google Scholar 

  • Nishio, M., and Narahashi, T. 1990, Ethanol enhancement of GABA-activated chloride current in rat dorsal root ganglion neurons, Brain Res., 518:283–286.

    Article  PubMed  CAS  Google Scholar 

  • Norseth, T., and Clarkson, T., 1970, Studies on the biotransformation of 203Hg labeled methylmercury chloride in rats, Arch. Environ, Health, 21:717–727.

    Article  CAS  Google Scholar 

  • Ogata, N., Vogel, S. M., and Narahashi, T., 1988, Lindane but not deltamethrin blocks a component of GABA-activated chloride channels, Faseb J., 2:2895–2900.

    PubMed  CAS  Google Scholar 

  • Omata, S., Sato, M., Sakimura, K., and Sugano, H., 1980, Time-dependent accumulation of inorganic mercury in subcellular fractions of kidney, liver, and brain of rats exposed to methylmercury, Arch. Toxicol., 44:231–241.

    Article  PubMed  CAS  Google Scholar 

  • Oortgiesen, M., van Kleef, R. G. D. M., and Vijverberg, H. P. M., 1990a, Novel type of ion channel activated by Pb2+, Cd2+ and Al3+ in cultured mouse neuroblastoma cells, J. Membrane Biol., 113:261–268.

    Article  CAS  Google Scholar 

  • Oortgiesen, M., van Kleef, R. G. D. M., Bajnath, R. B., and Vijverberg, H. P. M., 1990b, Nanomolar concentrations of lead selectively block neuronal nicotinic acetylcholine responses in mouse neuroblastoma cells, Toxicol. Appl. Pharmacol. 103:165–174.

    Article  PubMed  CAS  Google Scholar 

  • Paiement, J., and Joly, L. P., 1985, Effect of organic mercury on the electrical resistance of phosphatidylserine bilayers, Biochim. Biophys. Acta, 816:179–181.

    Article  PubMed  CAS  Google Scholar 

  • Partridge, L. D., and Swandula, D., 1988, Calcium-activated non-specific cation channels, Trends in Neurosciences, 11:69–72.

    Article  PubMed  CAS  Google Scholar 

  • Quandt, F. N., Kato, E., and Narahashi, T., 1982, Effects of methylmercury on electrical responses of neuroblastoma cells, NeuroToxicology, 3:205–220.

    PubMed  CAS  Google Scholar 

  • Rustam, H., Von Burg, R., Amin-Zaki, L., and El Hassani, S., 1975, Evidence for a neuromuscular disorder in methylmercury poisoning, Arch. Environ. Health, 30:190–195.

    Article  PubMed  CAS  Google Scholar 

  • Shrivastav, B. B., Brodwick, M. S., and Narahashi, T., 1976, Methylmercury: Effects on electrical properties of squid axon membranes, Life Sci., 18:1077–1082.

    Article  PubMed  CAS  Google Scholar 

  • Skerfving, S., 1972, Organic mercury compounds. Relation between exposure and effects, in “Mercury in the Environment,” L. Friberg and J. Vostal, eds., 141–168, CRC Press, Cleveland.

    Google Scholar 

  • Skerritt, J. H., and Macdonald, R. L., 1984, Diazepam enhances the action but not the binding of the GABA analog THIP, Brain Res., 297:181–186.

    Article  PubMed  CAS  Google Scholar 

  • Snyder, R. D., and Seelinge, D. F., 1976, Methylmercury poisoning clinical follow up and sensory nerve conduction studies, J. Neurol. Neurosurg. Psychol., 39:701–704.

    Article  CAS  Google Scholar 

  • Somjen, G. G., Herman, S. P., and Klein, R., 1973, Electrophysiology of methyl mercury poisoning, J. Pharmacol. Exp. Ther., 186:579–592.

    PubMed  CAS  Google Scholar 

  • Swandulla, D., and Lux, H. D., 1985, Activation of a nonspecific cation conductance by intracellular Ca2+ elevation in bursting pacemaker neurons of Helix pomatia, J. Neurophysiol., 54:1430–1444.

    PubMed  CAS  Google Scholar 

  • Takeuchi, T., Morikawa, N., Matsumoto, H., and Shiraishi, Y., 1962, A pathological study of Minamata disease in Japan, Acta Neuropathol., 2:40–57.

    Article  Google Scholar 

  • Takeuchi, T., Matsumoto, H., Sasaki, M., Kambara, T., Shiraishi, Y., Hirata, Y., Nobuhiro, M., and Ito, H., 1968, Pathology of Minamata disease, Kumamato Med. J., 34:521–524.

    Google Scholar 

  • Traxinger, D. L., and Atchison, W. D., 1987, Comparative effects of divalent cations on the methylmercury-induced alterations of acetycholine release, J. Pharmacol. Exp. Ther., 240:451–459.

    PubMed  CAS  Google Scholar 

  • Von Burg, R., and Rustam, H., 1974, Conduction velocities in methylmercury poisoned patients, Bull. Environ. Contam. Toxicol., 12:81–85.

    Article  Google Scholar 

  • Von Burg, R., Northington, F. K., and Shamoo, A., 1980, Methylmercury inhibition of rat brain muscarinic receptors, Toxicol. Appl. Pharmacol., 53:285–292.

    Article  Google Scholar 

  • Weinreich, D., and Wonderlin, W. F., 1987, Copper activates a unique inward current in molluscan neurones, J. Physiol. (London), 394:429–443.

    CAS  Google Scholar 

  • Yellen, G., 1982, Single Ca2-activated nonselective cation channels in neuroblastoma, Nature (London) 296:357–359.

    Article  CAS  Google Scholar 

  • Yoshino, Y, Mozai, T., and Nakao, K., 1966, Distribution of mercury in the brain and its subcellular units in experimental organic mercury poisonings, J. Neurochem., 13:397–406.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois, USA

    Toshio Narahashi, Osamu Arakawa & Masanobu Nakahiro

Authors
  1. Toshio Narahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osamu Arakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masanobu Nakahiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Tokyo, Tokyo, Japan

    Tsuguyoshi Suzuki

  2. Kitasoto University, Tokyo, Japan

    Nobumasa Imura

  3. University of Rochester School of Medicine, Rochester, New York, USA

    Thomas W. Clarkson

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Narahashi, T., Arakawa, O., Nakahiro, M. (1991). Role of Neuronal Ion Channels in Mercury Intoxication. In: Suzuki, T., Imura, N., Clarkson, T.W. (eds) Advances in Mercury Toxicology. Rochester Series on Environmental Toxicity. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9071-9_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9071-9_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9073-3

  • Online ISBN: 978-1-4757-9071-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation