Advertisement

Journal of Bioenergetics and Biomembranes

, Volume 35, Issue 6, pp 697–718 | Cite as

Ca2+ Channels as Targets of Neurological Disease: Lambert–Eaton Syndrome and Other Ca2+ Channelopathies

  • Michael T. Flink
  • William D. AtchisonEmail author
Article

Abstract

In the nervous system, voltage-gated Ca2+ channels regulate numerous processes critical to neuronal function including secretion of neurotransmitters, initiation of action potentials in dendritic regions of some neurons, growth cone elongation, and gene expression. Because of the critical role which Ca2+ channels play in signaling processes within the nervous system, disruption of their function will lead to profound disturbances in neuronal function. Voltage-gated Ca2+ channels are the targets of several relatively rare neurological or neuromuscular diseases resulting from spontaneously-occurring mutations in genes encoding for parts of the channel proteins, or from autoimmune attack on the channel protein responses. Mutations in CACNA1A, which encodes for the α1A subunit of P/Q-type Ca2+ channels, lead to symptoms seen in familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6. Conversely, autoimmune attack on Ca2+ channels at motor axon terminals causes peripheral cholinergic nerve dysfunction observed in Lambert–Eaton Myasthenic Syndrome (LEMS), the best studied of the disorders targeting voltage-gated Ca2+ channels. LEMS is characterized by decreased evoked quantal release of acetylcholine (ACh) and disruption of the presynaptic active zones, the sites at which ACh is thought to be released. LEMS is generally believed to be due to circulating antibodies directed specifically at the Ca2+ channels located at or near the active zone of motor nerve terminals (P/Q-type) and hence involved in the release of ACh. However, other presynaptic proteins have also been postulated to be targets of the autoantibodies. LEMS has a high degree of coincidence (∼60%) with small cell lung cancer; the remaining 40% of patients with LEMS have no detectable tumor. Diagnosis of LEMS relies on characteristic patterns of electromyographic changes; these changes are observable at neuromuscular junctions of muscle biopsies from patients with LEMS. In the majority of LEMS patients, those having detectable tumor, the disease is thought to occur as a result of immune response directed initially against voltage-gated Ca2+ channels found on the lung tumor cells. In these patients, effective treatment of the underlying tumor generally causes marked improvement of the symptoms of LEMS as well. Animal models of LEMS can be generated by chronic administration of plasma, serum or immunoglobulin G to mice. These models have helped dramatically in our understanding of the pathogenesis of LEMS. This “passive transfer” model mimics the electrophysiological and ultrastructural findings seen in muscle biopsies of patients with LEMS. In this model, we have shown that the reduction in amplitude of Ca2+ currents through P/Q-type channels is followed by “unmasking” of an L-type Ca2+ current not normally found at the motor nerve terminal which participates in release of ACh from terminals of mice treated with plasma from patients with LEMS. It is unclear what mechanisms underlie the development of this novel L-type Ca2+ current involved in release of ACh at motor nerve terminals during passive transfer of LEMS.

Lambert–Eaton syndrome myasthenic syndromes motor nerve terminal neuromuscular junction neuromuscular diseases Ca channelopathy acetylcholine release dihydropyridine neuromuscular transmission 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Augustine, G. J., Charlton, M. P., and Smith, S. J., (1987). Annu. Rev. Neurosci. 10, 633–693.PubMedGoogle Scholar
  2. Baker, P. F., and Crawford, A. C., (1975). J. Physiol. (Lond.), 247, 209–226.Google Scholar
  3. Barclay, J., Balaguero, N., Mione, M., Ackerman, S. L., Letts, V. A., Brodbeck, J., Canti, C., Meir, A., Page, K. M., Kusumi, K., Perez-Reyes, E., Lander, E. S., Frankel, W. N., Gardiner, R. M., Dolphin, A. C., and Rees, M., (2001). J. Neurosci. 21, 6095–6104.PubMedGoogle Scholar
  4. Barry, E. L., Viglione, M. P., Kim, Y. I., and Froehner, S. C., (1995). J. Neurosci. 15, 274–283.PubMedGoogle Scholar
  5. Benjamini, E., Sunshine, G., and Leskowitz, S., (1996). In, Immunology 3rd edn. (Benjamini, E., Sunshine, G., and Leskowitz, S., eds.), Wiley-Liss, New York, pp. 245–259.Google Scholar
  6. Blandino, J. K., and Kim, Y. I., (1993). Ann. N. Y. Acad. Sci. 681, 394–397.PubMedGoogle Scholar
  7. Brice, N. L., Berrow, N. S., Campbell, V., Page, K. M., Brickley, K., Tedder, I., and Dolphin, A. C., (1997). Eur. J. Neurosci. 9, 749–759.PubMedGoogle Scholar
  8. Brice, N. L., Dolphin, A. C., (1999). J. Physiol. (Lond.), 515, 685–694.Google Scholar
  9. Brose, N., Petrenko, A. G., Südhof, T. C., and Jahn, R., (1992). Science, 256, 1021–1025.PubMedGoogle Scholar
  10. Bruera, E., Chadwick, S., Fox, R., Hanson, J., and MacDonald, N., (1986). Cancer Treat. Rep. 70, 1383–1387.PubMedGoogle Scholar
  11. Burgess, D. L., Jones, J. M., Meisler, M. H., and Noebels, J. L., (1997). Cell, 88, 385–392.PubMedGoogle Scholar
  12. Catterall, W. A., (2000). Annu. Rev. Cell Dev. Biol. 16, 521–555.PubMedGoogle Scholar
  13. Chalk, C. H., Murray, N. M., Newsom-Davis, J., O'Neill, J. H., and Spiro, S. G., (1990). Neurology, 40, 1552–1556.PubMedGoogle Scholar
  14. Chien, A. J., Zhao, X., Shirokov, R. E., Puri, T. S., Chang, C. F., Sun, D., Rios, E., and Hosey, M. M., (1995). J. Biol. Chem. 270, 30036–30044.PubMedGoogle Scholar
  15. Codignola, A., Tarroni, P., Clementi, F., Pollo, A., Lovallo, M., Carbone, E., Sher, E., (1993). J. Biol. Chem. 268, 26240–26247.PubMedGoogle Scholar
  16. Correia-de-Sa, P., Timoteo, M. A., and Ribeiro, J. A., (2000a). Eur. J. Pharmacol. 406, 355–362.PubMedGoogle Scholar
  17. Correia-de-Sa, P., Timoteo, M. A., and Ribeiro, J. A., (2000b). J. Neurochem. 74, 2462–2469.PubMedGoogle Scholar
  18. Cull-Candy, S. G., Miledi, R., Trautmann, A., and Uchitel, O. D., (1980). J. Physiol. (Lond.), 299, 621–638.Google Scholar
  19. Darnell, R. B., and DeAngelis, L. M., (1993). Lancet, 341, 21–22.PubMedGoogle Scholar
  20. David, P., Martin-Moutot, N., Leveque, C., el Far, O., Takahashi, M., and Seagar, M. J., (1993). Neuromuscul. Disord. 3, 451–454.PubMedGoogle Scholar
  21. De Aizpurua, H. J., Griesmann, G. E., Lambert, E. H., and Lennon, V. A., (1988). Ann. N. Y. Acad. Sci. 540, 369–371.PubMedGoogle Scholar
  22. De Luca, A., Rand, M. J., Reid, J. J., and Story, D. F., (1991). Toxicon, 29, 311–320.PubMedGoogle Scholar
  23. Dove, L. S., Abbott, L. C., and Griffith, W. H., (1998). J. Neurosci. 18, 7687–7699.PubMedGoogle Scholar
  24. Doyle, J., Ren, X., Lennon, G., and Stubbs, L., (1997). Mamm. Genome, 8, 113–120.PubMedGoogle Scholar
  25. Eaton, L. M., and Lambert, E. H., (1957). J. Am. Med. Assoc. 163, 1117–1124.PubMedGoogle Scholar
  26. el Far, O., Marqueze, B., Leveque, C., Martin-Moutot, N., Lang, B., Newsom-Davis, J., Yoshida, A., Takahashi, M., and Seagar, M. J., (1995). J. Neurochem. 64, 1696–1702.PubMedGoogle Scholar
  27. Elmqvist, D., and Lambert, E. H., (1968). Mayo Clin. Proc. 43, 689–713.PubMedGoogle Scholar
  28. Engel, A. G., Fukuoka, T., Lang, B., Newsom-Davis, J., Vincent, A., and Wray, D., (1987). Ann. N. Y. Acad. Sci. 505, 333–345.PubMedGoogle Scholar
  29. Engel, A. G., Lindstrom, J. M., Lambert, E. H., and Lennon, V. A., (1977). Neurology, 27, 307–315.PubMedGoogle Scholar
  30. Engel, A. G., and Santa, T., (1971). Ann. N. Y. Acad. Sci. 183, 46–63.PubMedGoogle Scholar
  31. Engisch, K. L., Rich, M. M., Cook, N., and Nowycky, M. C., (1999). J. Neurosci. 19, 3384–3395.PubMedGoogle Scholar
  32. Erlington, G., and Newsom-Davis, J., (1994). In, Handbook of Myasthenia Gravis and Myasthenic Syndromes (Lisak, R. P., ed.), Marcel Dekker, New York, pp. 81–102.Google Scholar
  33. Escayg, A., De Waard, M., Lee, D. D., Bichet, D., Wolf, P., Mayer, T., Johnston, J., Baloh, R., Sander, T., and Meisler, M. H., (2000). Am. J. Hum. Genet. 66, 1531–1539.PubMedGoogle Scholar
  34. Fletcher, C. F., Lutz, C. M., O'Sullivan, T. N., Shaughnessy, J. D., Jr., Hawkes, R., Frankel, W. N., Copeland, N. G., and Jenkins, N. A., (1996). Cell, 87, 607–617.PubMedGoogle Scholar
  35. Flink, M. F., and Atchison, W. D., (2002). J. Physiol. (Lond.), 543, (2), 567–576.Google Scholar
  36. Flink, M. F., and Atchison, W. D., (2003). J. Pharmacol. Exp. Ther. 305, 646–652.PubMedGoogle Scholar
  37. Fukunaga, H., (1982). Muscle Nerve, 5, 686–697.Google Scholar
  38. Fukunaga, H., Engel, A. G., Lang, B., Newsom-Davis, J., and Vincent, A., (1983). Proc. Natl. Acad. Sci. U.S.A. 80, 7636–7640.PubMedGoogle Scholar
  39. Fukuoka, T., Engel, A. G., Lang, B., Newsom-Davis, J., Prior, C., and Wray, D. W., (1987a). Ann. Neurol. 22, 193–199.PubMedGoogle Scholar
  40. Fukuoka, T., Engel, A. G., Lang, B., Newsom-Davis, J., and Vincent, A., (1987b). Ann. Neurol. 22, 200–211.PubMedGoogle Scholar
  41. Garcia, K. D., and Beam, K. G., (1996). J. Neurosci. 16, 4903–4913.PubMedGoogle Scholar
  42. Garcia, K. D., Mynlieff, M., Sanders, D. B., Beam, K. G., and Walrond, J. P., (1996). Proc. Natl. Acad. Sci. U.S.A. 93, 9264–9269.PubMedGoogle Scholar
  43. Goetz, O., (1987). In, The Complement Systemm (Rother Ka, T. O., ed.), Springer-Verlag, New York, pp. 154–168.Google Scholar
  44. Goetz, O., and Muller-Eberhand, H. J., (1971). J. Exp. Med. 134, 90–108.Google Scholar
  45. Gould, G. A., Ashworth, M., and Lewis, G. T., (1986). Thorax, 41, 372–375.PubMedGoogle Scholar
  46. Grassi, C., Magnelli, V., Carabelli, V., Sher, E., and Carbone, E., (1994). Neurosci. Lett. 181, 50–56.PubMedGoogle Scholar
  47. Gutmann, L., Crosby, T. W., Takamori, M., and Martin, J. D., (1972). Am. J. Med. 53, 354–356.PubMedGoogle Scholar
  48. Hafner, M., and Petzelt, C., (1987). Nature, 330, 264–266.PubMedGoogle Scholar
  49. Hajela, R. K., and Atchison, W. D., (1995). J. Neurochem. 64, 1245–1251.PubMedGoogle Scholar
  50. Heath, J. P., Ewing, D. J., and Cull, R. E., (1988). J. Neurol. Neurosurg. Psychia. 51, 436–439.Google Scholar
  51. Henriksson, K. G., Nilsson, O., Rosen, I., and Schiller, H. H., (1977). Acta Neurol. Scand. 56, 117–140.PubMedGoogle Scholar
  52. Herrup, K., and Wilczynski, S. L., (1982). Neuroscience, 7, 2185–2196.PubMedGoogle Scholar
  53. Hesselmans, L. F., Jennekens, F. G., Kartman, J., Wokke, J. H., de visser, M., Klaver-Krol, E. G., DeBaets, M., Spaans, F., and Veldman, H., (1992). Acta Neuropathol. 83, 202–206.PubMedGoogle Scholar
  54. Heuser, J. E., Reese, T. S., Dennis, M. J., Jan, Y., Jan, L., and Evans, L., (1979). J. Cell Biol. 81, 275–300.PubMedGoogle Scholar
  55. Hewett, S. J., and Atchison, W. D., (1991). Brain Res. 566, 320–324.PubMedGoogle Scholar
  56. Hewett, S. J., and Atchison, W. D., (1992a). Brain Res. 599, 324–332.Google Scholar
  57. Hewett, S. J., and Atchison, W. D., (1992b). Brain Res. 599, 317–323.PubMedGoogle Scholar
  58. Hirning, L. D., Fox, A. P., McCleskey, E. W., Olivera, B. M., Thayer, S. A., Miller, R. J., and Tsien, R. W., (1988). Science, 239, 57–61.PubMedGoogle Scholar
  59. Hong, S. J., and Chang, C. C., (1990). Br. J. Pharmacol. 101, 793–798.PubMedGoogle Scholar
  60. Hong, S. J., and Chang, C. C., (1995). Br. J. Pharmacol. 116, 1577–1582.PubMedGoogle Scholar
  61. Hostetter, M. K., Krueger, R. A., and Schmeling, D. J., (1984). J. Infect. Dis. 150, 653–661.PubMedGoogle Scholar
  62. Houzen, H., Hattori, Y., Kanno, M., Kikuchi, S., Tashiro, K., Motomura, M., Nakao, Y., and Nakamura, T., (1998). Ann. Neurol. 43, 677–680.PubMedGoogle Scholar
  63. Iwasa, K., Takamori, M., Komai, K., and Mori, Y., (2000). Neurology, 54, 757–759.PubMedGoogle Scholar
  64. Jablecki, C., (1984). Muscle Nerve, 7, 250–257.PubMedGoogle Scholar
  65. Jenkinson, D. H., (1957). J. Physiol. (Lond.), 138, 434–444.Google Scholar
  66. Johnston, I., Lang, B., Leys, K., and Newsom-Davis, J., (1994). Neurology, 44, 334–338.PubMedGoogle Scholar
  67. Jouvenceau, A., Eunson, L. H., Spauschus, A., Ramesh, V., Zuberi, S. M., Kullmann, D. M., and Hanna, M. G., (2001). Lancet, 358, 801–807.PubMedGoogle Scholar
  68. Katz, B., and Miledi, R., (1970). J. Physiol. (Lond.), 207, 789–801.Google Scholar
  69. Katz, E., Ferro, P. A., Cherksey, B. D., Sugimori, M., Llinas, R., and Uchital, O. D., (1995). J. Physiol. (Lond.), 486, 695–706.Google Scholar
  70. Katz, E., Ferro, P. A., Weisz, G., and Uchitel, O. D., (1996). J. Physiol. (Lond.), 497, 687–697.Google Scholar
  71. Keesey, J. C., (1989). Muscle Nerve, 12, 613–626.PubMedGoogle Scholar
  72. Khurana, R. K., Koski, C. L., and Mayer, R. F., (1988). J. Neurol. Sci. 85, 77–86.PubMedGoogle Scholar
  73. Kim, Y. I., (1985). Muscle Nerve, 8, 162–172.PubMedGoogle Scholar
  74. Kim, Y. I., (1987). Ann. N. Y. Acad. Sci. 505, 377–379.PubMedGoogle Scholar
  75. Kim, Y. I., Blandino, J. K., and O'Shaughnessy, T. J., (1993). Ann. N. Y. Acad. Sci. 681, 398–401.PubMedGoogle Scholar
  76. Kim, Y. I., Nam, T. S., Kim, S. H., Viglione, M. P., and Kim, J., (1998). Ann. N. Y. Acad. Sci. 841, 677–683.PubMedGoogle Scholar
  77. Kim, Y. I., and Neher, E., (1988). Science, 239, 405–408.PubMedGoogle Scholar
  78. Kim, Y. I., Sanders, D. B., Johns, T. R., Phillips, L. H., and Smith, R. E., (1988). J. Neurol. Sci. 87, 1–13.PubMedGoogle Scholar
  79. Komai, K., Iwasa, K., and Takamori, M., (1999). J. Neurol. Sci. 166, 126–130.PubMedGoogle Scholar
  80. Krendel, D. A., and Hopkins, L. C., (1986). Muscle Nerve, 9, 519–522.PubMedGoogle Scholar
  81. Lambert, E. H., and Elmqvist, D., (1971). Ann. N. Y. Acad. Sci. 183, 183–199.PubMedGoogle Scholar
  82. Lambert, E. H., and Lennon, V. A., (1988). Muscle Nerve, 11, 1133–1145.PubMedGoogle Scholar
  83. Lambert, E. H., and Rooke, E. D., (1965). In, The Remote Effects of Cancer on the Nervous System (Brian, L., and Norris, F. H., eds.), Grune and Statton, New York.Google Scholar
  84. Lambert, E. H., Rooke, E. D., and Eaton, L. M., (1961). In, Myasthenia Gravis, The 2nd International Symposium Proceedings (Viets, H. R., ed.) Charles C. Thomas, Springfield, IL.Google Scholar
  85. Lang, B., Molenaar, P. C., Newsom-Davis, J., and Vincent, A., (1984). J. Neurochem. 42, 658–662.PubMedGoogle Scholar
  86. Lang, B., Newsom-Davis, J., Peers, C., Prior, C., and Wray, D. W., (1987). J. Physiol. (Lond.), 390, 257–270.Google Scholar
  87. Lang, B., Newsom-Davis, J., Wray, D., Vincent, A., and Murray, N., (1981). Lancet, 2, 224–226.PubMedGoogle Scholar
  88. Lang, B., Vincent, A., Murray, N. M., and Newsom-Davis, J., (1989). Ann. Neurol. 25, 265–271.PubMedGoogle Scholar
  89. Lemos, J. R., Nowycky, M. C., (1989). Neuron, 2, 1419–1426.PubMedGoogle Scholar
  90. Lennon, V. A., Kryzer, T. J., Griesmann, G. E., O'Suilleabhain, P. E., Windebank, A. J., Woppmann, A., Miljanich, G. P., and Lambert, E. H., (1995). N. Engl. J. Med. 332, 1467–1474.PubMedGoogle Scholar
  91. Lennon, V. A., and Lambert, E. H., (1989). Mayo Clin. Proc. 64, 1498–1504.PubMedGoogle Scholar
  92. Lennon, V. A., Lambert, E. H., Whittingham, S., and Fairbanks, V., (1982). Muscle Nerve, 5, S21–S25.PubMedGoogle Scholar
  93. Leveque, C., Hoshino, T., David, P., Shoji-Kasai, Y., Leys, K., Omori, A., Lang, B., el Far, O., Sato, K., and Martin-Moutot, N., (1992). Proc. Natl. Acad. Sci. U.S.A. 89, 3625–3629.PubMedGoogle Scholar
  94. Leys, K., Lang, B., Johnston, I., and Newsom-Davis, J., (1991). Ann. Neurol. 29, 307–314.PubMedGoogle Scholar
  95. Leys, K., Lang, B., Vincent, A., and Newsom-Davis, J., (1989). Lancet, 2, 1107.Google Scholar
  96. Llinas, R., Steinberg, I. Z., and Walton, K., (1976). Proc. Natl. Acad. Sci. U.S.A. 73, 2913–2922.Google Scholar
  97. Loos, M., (1987). In, The Complement System (Rother Ka, T. O., ed.), Springer-Verlag, New York, pp. 136–141.Google Scholar
  98. Lorenzon, N. M., and Beam, K. G., (2000). Kidney Int. 57, 794–802.PubMedGoogle Scholar
  99. Magnelli, V., Grassi, C., Parlatore, E., Sher, E., and Carbone, E., (1996). FEBS. Lett. 387, 47–52.PubMedGoogle Scholar
  100. Maier, H. C., and Sommers, S. C., (1986). Ann. Thorac. Surg. 41, 560–562.PubMedGoogle Scholar
  101. Mamdani, M. B., Walsh, R. L., Rubino, F. A., Brannegan, R. T., and Hwang, M. H., (1985). J. Auton. Nerv. Syst. 12, 315–320.PubMedGoogle Scholar
  102. Martin-Moutot, N., Lang, B., Newsom-Davis, J., and Seagar, M., (1995). Neurosci. Lett. 187, 115–118.PubMedGoogle Scholar
  103. McCann, F. V., Pettengill, O. S., Cole, J. J., Russell, J. A., and Sorenson, G. D., (1981). Science, 212, 1155–1157.PubMedGoogle Scholar
  104. McCusker, C. T., and Singal, D. P., (1990). Transfus. Med. Rev. 4, 279–287.PubMedGoogle Scholar
  105. McEnery, M. W., Copeland, T. D., and Vanve, C. L., (1998). J. Biol. Chem. 273, 21435–21438.PubMedGoogle Scholar
  106. Meir, A., and Dolphin, A. C., (2002). Modulator (Alamone Labs, Israel), 16, 4–13.Google Scholar
  107. Meriney, S. D., Hulsizer, S. C., Lennon, V. A., and Grinnell, A. D., (1996). Ann. Neurol. 40, 739–749.PubMedGoogle Scholar
  108. Meyer, E. M., Momol, A. E., Kramer, B. S., Ross, W. E., and Scott, G., (1986). Biochem. Pharmacol. 35, 3412–3414.PubMedGoogle Scholar
  109. Mintz, I. M., Venema, V. J., Swiderek, K. M., Lee, T. D., Bean, B. P., and Adams, M. E., (1992). Nature, 355, 827–829.PubMedGoogle Scholar
  110. Moises, H. C., Rusin, K. I., and Macdonald, R. L., (1994). J. Neurosci. 14, 3842–3851.PubMedGoogle Scholar
  111. Molenaar, P. C., Newsom-Davis, J., Polak, R. L., and Vincent, A., (1982). Neurology, 32, 1061–1065.PubMedGoogle Scholar
  112. Mori, Y., Wakamori, M., Oda, S., Fletcher, C. F., Sekiguchi, N., Mori, E., Copeland, N. G., Jenkins, N. A., Matsushita, K., Matsuyama, Z., and Imoto, K., (2000). J. Neurosci. 20, 5654–5662.PubMedGoogle Scholar
  113. Motomura, M., Lang, B., Johnston, I., Palace, J., Vincent, A., and Newsom-Davis, J., (1997). J. Neurol. Sci. 147, 35–42.PubMedGoogle Scholar
  114. Mynlieff, M., and Beam, K. G., (1992). Dev. Biol. 152, 407–410.PubMedGoogle Scholar
  115. Nagel, A., Engel, A. G., Lang, B., Newsom-Davis, J., and Fukouka, T., (1998). Ann. Neurol. 24, 552–558.Google Scholar
  116. Neely, A., Wei, X., Olcese, R., Birnbaumer, L., and Stefani, E., (1993). Science, 262, 575–578.PubMedGoogle Scholar
  117. Newsom-Davis, J., and Murray, N. M., (1984). Neurology, 34, 480–485.PubMedGoogle Scholar
  118. Norris, F. H., Jr., and Panner, B. J., (1966). Arch. Neurol. 14, 574–589.PubMedGoogle Scholar
  119. Oh, S. J., Kim, D. S., Head, T. C., and Claussen, G. C., (1997). Muscle Nerve, 20, 1146–1152.PubMedGoogle Scholar
  120. O'Neill, J. H., Murray, N. M., and Newsom-Davis, J., (1998). Brain, 111, 577–596.Google Scholar
  121. Ophoff, R. A., Terwindt, G. M., Vergouwe, M. N., van Eijk, R., Oefner, P. J., Hoffman, S. M., Lamerdin, J. E., Mohrenweiser, H. W., Bulman, D. E., Ferrai, M., Hann, J., Lindhout, D., van Ommen, G. J., Hofker, M. H., and Ferrari, M. D., Frants R. R., (1996). Cell, 87, 543–552.PubMedGoogle Scholar
  122. Owen, P. J., Marriott, D. B., and Boarder, M. R., (1989). Br. J. Pharmacol. 97, 133–138.PubMedGoogle Scholar
  123. Pancrazio, J. J., Viglione, M. P., Tabbara, I. A., and Kim, Y. I., (1989). Cancer Res. 49, 5901–5906.PubMedGoogle Scholar
  124. Park, D. M., Johnson, R. H., Crean, G. P., and Robinson, J. F., (1972). Br. Med. J. 3, 510–511.PubMedGoogle Scholar
  125. Parsons, K. T., and Kwok, W. W., (2002). J. Neuroimmunol. 126, 190–195.PubMedGoogle Scholar
  126. Parsons, K. T., Kwok, W. W., and Gaur, L. K., Nepom G. T., (2002). Hum. Immunol. 61, 828–833.Google Scholar
  127. Peers, C., Johnston, I., Lang, B., and Wray, D., (1993). Neurosci. Lett. 153, 45–48.PubMedGoogle Scholar
  128. Peers, C., Lang, B., Newsom-Davis, J., and Wray, D. W., (1990). J. Physiol. (Lond.), 421, 293–308.Google Scholar
  129. Perin, M. S., Fried, V. A., Mignery, G. A., Jahn, R., and Südhof, T. C., (1990). Nature, 345, 260–263.PubMedGoogle Scholar
  130. Pietrobon, D., (2002). Mol. Neurobiol. 25, 31–50.PubMedGoogle Scholar
  131. Pinto, A., Gillard, S., Moss, F., Whyte, K., Brust, P., Williams, M., Stauderman, K., Harpold, M., Lang, B., Newsom-Davis, J., Bleakman, D., Lodge, D., and Boot, J., (1998). Proc. Natl. Acad. Sci. U.S.A. 95, 8328–8333.PubMedGoogle Scholar
  132. Pinto, A, Iwasa, K., Newland, C., Newsom-Davis, J., and Lang, B., (2002). Muscle Nerve, 25, 715–724.PubMedGoogle Scholar
  133. Porter, R. R., and Reid, K. B., (1978). Nature, 275, 699–704.PubMedGoogle Scholar
  134. Prior, C., Lang, B., Wray, D., and Newsom-Davis, J., (1985). Ann. Neurol. 17, 587–592.PubMedGoogle Scholar
  135. Protti, D. A., Reisin, R., Mackinley, T. A., and Uchitel, O. D., (1996). Neurology, 46, 1391–1396.PubMedGoogle Scholar
  136. Protti, D. A., and Uchitel, O. D., (1997). Pflügers Arch. 434, 406–412.Google Scholar
  137. Pumplin, D. W., Reese, T. S., and Llinas, R., (1981). Proc. Natl. Acad. Sci. U.S.A. 78, 7210–7213.PubMedGoogle Scholar
  138. Rammensee, H. G., Falk, K., and Rotzschke, O., (1993). Curr. Opin. Immunol. 5, 35–44.PubMedGoogle Scholar
  139. Roberts, A., Perera, S., Lang, B., Vincent, A., and Newsom-Davis, J., (1985). Nature, 317, 737–739.PubMedGoogle Scholar
  140. Robinson, I. M., Finnegan, J. M., Monck, J. R., Wightman, R. M., and Fernandez, J. M., (1995). Proc. Natl. Acad. Sci. U.S.A. 92, 2474–2478.PubMedGoogle Scholar
  141. Robitaille, R., Adler, E. M., and Charlton, M. P., (1990). Neuron, 5, 773–779.PubMedGoogle Scholar
  142. Robitaille, R., and Charlton, M. P., (1992). J. Neurosci. 12, 297–305.PubMedGoogle Scholar
  143. Robitaille, R., Garcia, M. L., Kaczorowski, G. J., and Charlton, M. P., (1993). Neuron, 11, 645–655.PubMedGoogle Scholar
  144. Rosato-Siri, M. D., Piriz, J., Tropper, B. A., and Uchitel, O. D., (2002). Eur. J. Neurosci. 15, 1874–1880.PubMedGoogle Scholar
  145. Rosato-Siri, M. D., and Uchitel, O. D., (1999). J. Physiol. (Lond.), 514, 533–540.Google Scholar
  146. Rosenfeld, M. R., Wong, E., Dalmau, J., Manley, G., Egan, D., Posner, J. B., Sher, E., Furneaux, H. M., (1993b). Ann. N. Y. Acad. Sci. 681, 408–411.PubMedGoogle Scholar
  147. Rosenfeld, M. R., Wong, E., Dalmau, J., Manley, G., Posner, J. B., Sher, E., Furneaux, H. M., (1993a). Ann. Neurol. 33, 113–120.PubMedGoogle Scholar
  148. Rubenstein, A. E., Horowitz, S. H., and Bender, A. N., (1979). Neurology, 29, 720–723.PubMedGoogle Scholar
  149. Sanders, D. B., (1994). Handbook of Myasthenia Gravis and Myasthenic Syndromes Marcell Dekker, New York, pp. 103–148.Google Scholar
  150. Sanders, D. B., (1998). Ann. N. Y. Acad. Sci. 841, 811–816.PubMedGoogle Scholar
  151. Sanders, D. B., Massey, J. M., Sanders, L. L., and Edwards, L. J., (2000). Neurology, 54, 603–607.PubMedGoogle Scholar
  152. Sano, K., Enomoto, K., and Maeno, T., (1987). Eur. J. Pharmacol. 141, 235–241.PubMedGoogle Scholar
  153. Santafe, M. M., Garcia, N., Lanuza, M. A., Uchitel, O. D., and Salon, I., Tomas J., (2002). Neuroscience, 110, 147–154.PubMedGoogle Scholar
  154. Santafe, M. M., Garcia, N., Lanuza, M. A., Uchitel, O. D., and Tomas, J., (2001). Neuroscience, 102, 697–708.PubMedGoogle Scholar
  155. Santafe, M. M., Urbano, F. J., Lanuza, M. A., Uchitel, O. D., (2000). Neuroscience, 95, 227–234.PubMedGoogle Scholar
  156. Satoh, Y., Hirashima, N., Tokumaru, H., Takahashi, M. P., Kang, J., Viglione, M. P., Kim, Y. I., and Kirino, Y., (1998). J. Physiol. (Lond.), 508, 427–438.Google Scholar
  157. Sculptoreanu, A., Figourov, A., and De Groat, W. C., (1995). Am. J. Physiol. 269, C725–C732.PubMedGoogle Scholar
  158. Sculptoreanu, A., Yoshimura, N., de Groat, W. C., and Somogyi, G. T., (2001). Neurochem. Res. 26, 933–942.PubMedGoogle Scholar
  159. Sher, E., Carbone, E., and Clementi, F., (1993). Ann. N. Y. Acad. Sci. 681, 373–381.PubMedGoogle Scholar
  160. Sher, E., Gotti, C., Canal, N., Scoppetta, C., Piccolo, G., Evoli, A., Clementi, F., (1989). Lancet, 2, 640–643.PubMedGoogle Scholar
  161. Sher, E., Pandiella, A., and Clementi, F., (1990). Cancer Res. 50, 3892–3896.PubMedGoogle Scholar
  162. Shoji-Kasai, Y., Yoshida, A., Sato, K., Hoshino, T., Ogura, A., Kondo, S., Fujimoto, Y., Kuwahara, R., Kato, R., Takahashi, M., (1992). Science, 256, 1821–1823.PubMedGoogle Scholar
  163. Silinsky, E. M., (1985). Pharmacol. Rev. 37, 81–132.PubMedGoogle Scholar
  164. Singer, D., Biel, M., Lotan, I., Flockerzi, V., Hofmann, F., and Dascal, N., (1991). Science, 253, 1553–1557.PubMedGoogle Scholar
  165. Smith, D. O., Conklin, M. W., Jensen, P. J., and Atchison, W. D., (1995). J. Physiol. (Lond.), 487, 115–123.Google Scholar
  166. Suenaga, A., Shirabe, S., Nakamura, T., Motomura, M., Tsujihata, M., Matsuo, H., Kataoka, Y., Niwa, M., Itoh, M., and Nagataki, S., (1996). Muscle Nerve, 19, 1166–1168.PubMedGoogle Scholar
  167. Sugiura, Y., and Ko, C. P., (1997). J. Neurosci. 17, 1101–1111.PubMedGoogle Scholar
  168. Takamori, M., Gutmann, L., Crosby, T. W., and Martin, J. D., (1972). Arch. Neurol. 26, 326–335.PubMedGoogle Scholar
  169. Takamori, M., Hamada, T., Komai, K., Takahashi, M., and Yoshida, A., (1994). Ann. Neurol. 35, 74–80.PubMedGoogle Scholar
  170. Takamori, M., Hamada, T., and Okumura, S., (1992). J. Neurol. Sci. 109, 182–187.PubMedGoogle Scholar
  171. Takamori, M., Iwasa, K., and Komai, K., (1997). Neurology, 48, 1261–1265.PubMedGoogle Scholar
  172. Takamori, M., Komai, K., and Iwasa, K., (2000a). Am. J. Med. Sci. 319, 204–208.PubMedGoogle Scholar
  173. Takamori, M., Maruta, T., and Kamai, K., (2000b). Neurosci. Res. 36, 183–191.PubMedGoogle Scholar
  174. Takamori, M., Okumura, S., Komai, K., and Satake, R., (1990). J. Neurol. Sci. 99, 219–227.PubMedGoogle Scholar
  175. Takamori, M., Takahashi, M., Yasukawa, Y., Iwasa, K., Nemoto, Y., Suenaga, A., Nagataki, S., and Nakamura, T., (1995). J. Neurol. Sci. 133, 95–101.PubMedGoogle Scholar
  176. Talley, E. M., Sadr, N. N., and Bayliss, D., (1997). J. Neurosci. 17, 4473–4485.PubMedGoogle Scholar
  177. Tareilus, E., Schoch, J., and Breer, H., (1994). J. Neurochem. 62, 2283–2291.PubMedGoogle Scholar
  178. Tsujihata, M., Kinoshita, I., Mori, M., Mori, K., Shirabe, S., Satoh, A., and Nagataki, S., (1987). J. Neurol. Sci. 81, 197–213.PubMedGoogle Scholar
  179. Ueno, S., and Hara, Y., (1992). J. Neurol. Neurosurg. Psychia. 55, 409–410.Google Scholar
  180. Urbano, F. J., Depetris, R. S., and Uchitel, O. D., (2001). Pflügers Arch. 441, 824–831.Google Scholar
  181. Verschuuren, J. J., Dalmau, J., Tunkel, R., Lang, B., Graus, F., Schramm, L., Posner, J. B., Newsom-Davis, J., and Rosenfeld, M. R., (1998). Neurology, 50, 475–479PubMedGoogle Scholar
  182. Viglione, M. P., O'Shaughnessy, T. J., and Kim, Y. I., (1995). J. Physicol. (Lond.), 488, 303–317.Google Scholar
  183. Waterman, S. A., (1996). J. Neurosci. 16, 4155–4161.PubMedGoogle Scholar
  184. Waterman, S. A., (1997). Br. J. Pharmacol. 120, 393–398.PubMedGoogle Scholar
  185. Waterman, S. A., Lang, B., Newsom-Davis, J., (1997). Ann. Neurol. 42, 147–156.PubMedGoogle Scholar
  186. Wessler, I., Dooley, D. J., Osswald, H., and Schlemmer, F., (1990). Neurosci. Lett. 108, 173–178.PubMedGoogle Scholar
  187. Willcox, N., Demaine, A. G., Newsom-Davis, J., Welsh, K. I., Robb, S. A., and Spiro, S. G., (1985). Hum. Immunol. 14, 29–36.PubMedGoogle Scholar
  188. Wirtz, P. W., Roep, B. O., Schreuder, G. M., van Doorn, P. A., van Engelen, B. G., Kuks, J. B., Twijnstra, A., de Visser, M., Visser, L. H., Wokke, J. H., and Wintzen, A. R., Verschuuren J. J., (2001). Hum. Immunol. 62, 809–813.PubMedGoogle Scholar
  189. Wise, R. P., and MacDermot, V., (1962). J. Neurol. Neurosurg. Psychiatry, 25, 31–39.PubMedGoogle Scholar
  190. Wisgirda, M. E., and Dryer, S. E., (1994). Proc. Natl. Acad. Sci. U.S.A. 91, 2858–2862.PubMedGoogle Scholar
  191. Wray, D. W., Peers, C., Lang, B., Lande, S., and Newsom-Davis, J., (1987). Ann. N. Y. Acad. Sci. 505, 368–376.PubMedGoogle Scholar
  192. Xu, Y. F., and Atchison, W. D., (1996). J. Pharmacol. Exp. Ther. 279, 1229–1236.PubMedGoogle Scholar
  193. Xu, Y. F., Hewett, S. J., and Atchison, W. D., (1998). J. Neurophysiol. 80, 1056–1069.PubMedGoogle Scholar
  194. Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., and Lee, C. C., (1997). Nat. Genet. 15, 62–69.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyMichigan State UniversityEast Lansing

Personalised recommendations