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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Augustine, G. J., Charlton, M. P., and Smith, S. J., (1987). Annu. Rev. Neurosci. 10, 633–693.
Baker, P. F., and Crawford, A. C., (1975). J. Physiol. (Lond.), 247, 209–226.
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.
Barry, E. L., Viglione, M. P., Kim, Y. I., and Froehner, S. C., (1995). J. Neurosci. 15, 274–283.
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.
Blandino, J. K., and Kim, Y. I., (1993). Ann. N. Y. Acad. Sci. 681, 394–397.
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.
Brice, N. L., Dolphin, A. C., (1999). J. Physiol. (Lond.), 515, 685–694.
Brose, N., Petrenko, A. G., Südhof, T. C., and Jahn, R., (1992). Science, 256, 1021–1025.
Bruera, E., Chadwick, S., Fox, R., Hanson, J., and MacDonald, N., (1986). Cancer Treat. Rep. 70, 1383–1387.
Burgess, D. L., Jones, J. M., Meisler, M. H., and Noebels, J. L., (1997). Cell, 88, 385–392.
Catterall, W. A., (2000). Annu. Rev. Cell Dev. Biol. 16, 521–555.
Chalk, C. H., Murray, N. M., Newsom-Davis, J., O'Neill, J. H., and Spiro, S. G., (1990). Neurology, 40, 1552–1556.
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.
Codignola, A., Tarroni, P., Clementi, F., Pollo, A., Lovallo, M., Carbone, E., Sher, E., (1993). J. Biol. Chem. 268, 26240–26247.
Correia-de-Sa, P., Timoteo, M. A., and Ribeiro, J. A., (2000a). Eur. J. Pharmacol. 406, 355–362.
Correia-de-Sa, P., Timoteo, M. A., and Ribeiro, J. A., (2000b). J. Neurochem. 74, 2462–2469.
Cull-Candy, S. G., Miledi, R., Trautmann, A., and Uchitel, O. D., (1980). J. Physiol. (Lond.), 299, 621–638.
Darnell, R. B., and DeAngelis, L. M., (1993). Lancet, 341, 21–22.
David, P., Martin-Moutot, N., Leveque, C., el Far, O., Takahashi, M., and Seagar, M. J., (1993). Neuromuscul. Disord. 3, 451–454.
De Aizpurua, H. J., Griesmann, G. E., Lambert, E. H., and Lennon, V. A., (1988). Ann. N. Y. Acad. Sci. 540, 369–371.
De Luca, A., Rand, M. J., Reid, J. J., and Story, D. F., (1991). Toxicon, 29, 311–320.
Dove, L. S., Abbott, L. C., and Griffith, W. H., (1998). J. Neurosci. 18, 7687–7699.
Doyle, J., Ren, X., Lennon, G., and Stubbs, L., (1997). Mamm. Genome, 8, 113–120.
Eaton, L. M., and Lambert, E. H., (1957). J. Am. Med. Assoc. 163, 1117–1124.
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.
Elmqvist, D., and Lambert, E. H., (1968). Mayo Clin. Proc. 43, 689–713.
Engel, A. G., Fukuoka, T., Lang, B., Newsom-Davis, J., Vincent, A., and Wray, D., (1987). Ann. N. Y. Acad. Sci. 505, 333–345.
Engel, A. G., Lindstrom, J. M., Lambert, E. H., and Lennon, V. A., (1977). Neurology, 27, 307–315.
Engel, A. G., and Santa, T., (1971). Ann. N. Y. Acad. Sci. 183, 46–63.
Engisch, K. L., Rich, M. M., Cook, N., and Nowycky, M. C., (1999). J. Neurosci. 19, 3384–3395.
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.
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.
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.
Flink, M. F., and Atchison, W. D., (2002). J. Physiol. (Lond.), 543, (2), 567–576.
Flink, M. F., and Atchison, W. D., (2003). J. Pharmacol. Exp. Ther. 305, 646–652.
Fukunaga, H., (1982). Muscle Nerve, 5, 686–697.
Fukunaga, H., Engel, A. G., Lang, B., Newsom-Davis, J., and Vincent, A., (1983). Proc. Natl. Acad. Sci. U.S.A. 80, 7636–7640.
Fukuoka, T., Engel, A. G., Lang, B., Newsom-Davis, J., Prior, C., and Wray, D. W., (1987a). Ann. Neurol. 22, 193–199.
Fukuoka, T., Engel, A. G., Lang, B., Newsom-Davis, J., and Vincent, A., (1987b). Ann. Neurol. 22, 200–211.
Garcia, K. D., and Beam, K. G., (1996). J. Neurosci. 16, 4903–4913.
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.
Goetz, O., (1987). In, The Complement Systemm (Rother Ka, T. O., ed.), Springer-Verlag, New York, pp. 154–168.
Goetz, O., and Muller-Eberhand, H. J., (1971). J. Exp. Med. 134, 90–108.
Gould, G. A., Ashworth, M., and Lewis, G. T., (1986). Thorax, 41, 372–375.
Grassi, C., Magnelli, V., Carabelli, V., Sher, E., and Carbone, E., (1994). Neurosci. Lett. 181, 50–56.
Gutmann, L., Crosby, T. W., Takamori, M., and Martin, J. D., (1972). Am. J. Med. 53, 354–356.
Hafner, M., and Petzelt, C., (1987). Nature, 330, 264–266.
Hajela, R. K., and Atchison, W. D., (1995). J. Neurochem. 64, 1245–1251.
Heath, J. P., Ewing, D. J., and Cull, R. E., (1988). J. Neurol. Neurosurg. Psychia. 51, 436–439.
Henriksson, K. G., Nilsson, O., Rosen, I., and Schiller, H. H., (1977). Acta Neurol. Scand. 56, 117–140.
Herrup, K., and Wilczynski, S. L., (1982). Neuroscience, 7, 2185–2196.
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.
Heuser, J. E., Reese, T. S., Dennis, M. J., Jan, Y., Jan, L., and Evans, L., (1979). J. Cell Biol. 81, 275–300.
Hewett, S. J., and Atchison, W. D., (1991). Brain Res. 566, 320–324.
Hewett, S. J., and Atchison, W. D., (1992a). Brain Res. 599, 324–332.
Hewett, S. J., and Atchison, W. D., (1992b). Brain Res. 599, 317–323.
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.
Hong, S. J., and Chang, C. C., (1990). Br. J. Pharmacol. 101, 793–798.
Hong, S. J., and Chang, C. C., (1995). Br. J. Pharmacol. 116, 1577–1582.
Hostetter, M. K., Krueger, R. A., and Schmeling, D. J., (1984). J. Infect. Dis. 150, 653–661.
Houzen, H., Hattori, Y., Kanno, M., Kikuchi, S., Tashiro, K., Motomura, M., Nakao, Y., and Nakamura, T., (1998). Ann. Neurol. 43, 677–680.
Iwasa, K., Takamori, M., Komai, K., and Mori, Y., (2000). Neurology, 54, 757–759.
Jablecki, C., (1984). Muscle Nerve, 7, 250–257.
Jenkinson, D. H., (1957). J. Physiol. (Lond.), 138, 434–444.
Johnston, I., Lang, B., Leys, K., and Newsom-Davis, J., (1994). Neurology, 44, 334–338.
Jouvenceau, A., Eunson, L. H., Spauschus, A., Ramesh, V., Zuberi, S. M., Kullmann, D. M., and Hanna, M. G., (2001). Lancet, 358, 801–807.
Katz, B., and Miledi, R., (1970). J. Physiol. (Lond.), 207, 789–801.
Katz, E., Ferro, P. A., Cherksey, B. D., Sugimori, M., Llinas, R., and Uchital, O. D., (1995). J. Physiol. (Lond.), 486, 695–706.
Katz, E., Ferro, P. A., Weisz, G., and Uchitel, O. D., (1996). J. Physiol. (Lond.), 497, 687–697.
Keesey, J. C., (1989). Muscle Nerve, 12, 613–626.
Khurana, R. K., Koski, C. L., and Mayer, R. F., (1988). J. Neurol. Sci. 85, 77–86.
Kim, Y. I., (1985). Muscle Nerve, 8, 162–172.
Kim, Y. I., (1987). Ann. N. Y. Acad. Sci. 505, 377–379.
Kim, Y. I., Blandino, J. K., and O'Shaughnessy, T. J., (1993). Ann. N. Y. Acad. Sci. 681, 398–401.
Kim, Y. I., Nam, T. S., Kim, S. H., Viglione, M. P., and Kim, J., (1998). Ann. N. Y. Acad. Sci. 841, 677–683.
Kim, Y. I., and Neher, E., (1988). Science, 239, 405–408.
Kim, Y. I., Sanders, D. B., Johns, T. R., Phillips, L. H., and Smith, R. E., (1988). J. Neurol. Sci. 87, 1–13.
Komai, K., Iwasa, K., and Takamori, M., (1999). J. Neurol. Sci. 166, 126–130.
Krendel, D. A., and Hopkins, L. C., (1986). Muscle Nerve, 9, 519–522.
Lambert, E. H., and Elmqvist, D., (1971). Ann. N. Y. Acad. Sci. 183, 183–199.
Lambert, E. H., and Lennon, V. A., (1988). Muscle Nerve, 11, 1133–1145.
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.
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.
Lang, B., Molenaar, P. C., Newsom-Davis, J., and Vincent, A., (1984). J. Neurochem. 42, 658–662.
Lang, B., Newsom-Davis, J., Peers, C., Prior, C., and Wray, D. W., (1987). J. Physiol. (Lond.), 390, 257–270.
Lang, B., Newsom-Davis, J., Wray, D., Vincent, A., and Murray, N., (1981). Lancet, 2, 224–226.
Lang, B., Vincent, A., Murray, N. M., and Newsom-Davis, J., (1989). Ann. Neurol. 25, 265–271.
Lemos, J. R., Nowycky, M. C., (1989). Neuron, 2, 1419–1426.
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.
Lennon, V. A., and Lambert, E. H., (1989). Mayo Clin. Proc. 64, 1498–1504.
Lennon, V. A., Lambert, E. H., Whittingham, S., and Fairbanks, V., (1982). Muscle Nerve, 5, S21–S25.
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.
Leys, K., Lang, B., Johnston, I., and Newsom-Davis, J., (1991). Ann. Neurol. 29, 307–314.
Leys, K., Lang, B., Vincent, A., and Newsom-Davis, J., (1989). Lancet, 2, 1107.
Llinas, R., Steinberg, I. Z., and Walton, K., (1976). Proc. Natl. Acad. Sci. U.S.A. 73, 2913–2922.
Loos, M., (1987). In, The Complement System (Rother Ka, T. O., ed.), Springer-Verlag, New York, pp. 136–141.
Lorenzon, N. M., and Beam, K. G., (2000). Kidney Int. 57, 794–802.
Magnelli, V., Grassi, C., Parlatore, E., Sher, E., and Carbone, E., (1996). FEBS. Lett. 387, 47–52.
Maier, H. C., and Sommers, S. C., (1986). Ann. Thorac. Surg. 41, 560–562.
Mamdani, M. B., Walsh, R. L., Rubino, F. A., Brannegan, R. T., and Hwang, M. H., (1985). J. Auton. Nerv. Syst. 12, 315–320.
Martin-Moutot, N., Lang, B., Newsom-Davis, J., and Seagar, M., (1995). Neurosci. Lett. 187, 115–118.
McCann, F. V., Pettengill, O. S., Cole, J. J., Russell, J. A., and Sorenson, G. D., (1981). Science, 212, 1155–1157.
McCusker, C. T., and Singal, D. P., (1990). Transfus. Med. Rev. 4, 279–287.
McEnery, M. W., Copeland, T. D., and Vanve, C. L., (1998). J. Biol. Chem. 273, 21435–21438.
Meir, A., and Dolphin, A. C., (2002). Modulator (Alamone Labs, Israel), 16, 4–13.
Meriney, S. D., Hulsizer, S. C., Lennon, V. A., and Grinnell, A. D., (1996). Ann. Neurol. 40, 739–749.
Meyer, E. M., Momol, A. E., Kramer, B. S., Ross, W. E., and Scott, G., (1986). Biochem. Pharmacol. 35, 3412–3414.
Mintz, I. M., Venema, V. J., Swiderek, K. M., Lee, T. D., Bean, B. P., and Adams, M. E., (1992). Nature, 355, 827–829.
Moises, H. C., Rusin, K. I., and Macdonald, R. L., (1994). J. Neurosci. 14, 3842–3851.
Molenaar, P. C., Newsom-Davis, J., Polak, R. L., and Vincent, A., (1982). Neurology, 32, 1061–1065.
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.
Motomura, M., Lang, B., Johnston, I., Palace, J., Vincent, A., and Newsom-Davis, J., (1997). J. Neurol. Sci. 147, 35–42.
Mynlieff, M., and Beam, K. G., (1992). Dev. Biol. 152, 407–410.
Nagel, A., Engel, A. G., Lang, B., Newsom-Davis, J., and Fukouka, T., (1998). Ann. Neurol. 24, 552–558.
Neely, A., Wei, X., Olcese, R., Birnbaumer, L., and Stefani, E., (1993). Science, 262, 575–578.
Newsom-Davis, J., and Murray, N. M., (1984). Neurology, 34, 480–485.
Norris, F. H., Jr., and Panner, B. J., (1966). Arch. Neurol. 14, 574–589.
Oh, S. J., Kim, D. S., Head, T. C., and Claussen, G. C., (1997). Muscle Nerve, 20, 1146–1152.
O'Neill, J. H., Murray, N. M., and Newsom-Davis, J., (1998). Brain, 111, 577–596.
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.
Owen, P. J., Marriott, D. B., and Boarder, M. R., (1989). Br. J. Pharmacol. 97, 133–138.
Pancrazio, J. J., Viglione, M. P., Tabbara, I. A., and Kim, Y. I., (1989). Cancer Res. 49, 5901–5906.
Park, D. M., Johnson, R. H., Crean, G. P., and Robinson, J. F., (1972). Br. Med. J. 3, 510–511.
Parsons, K. T., and Kwok, W. W., (2002). J. Neuroimmunol. 126, 190–195.
Parsons, K. T., Kwok, W. W., and Gaur, L. K., Nepom G. T., (2002). Hum. Immunol. 61, 828–833.
Peers, C., Johnston, I., Lang, B., and Wray, D., (1993). Neurosci. Lett. 153, 45–48.
Peers, C., Lang, B., Newsom-Davis, J., and Wray, D. W., (1990). J. Physiol. (Lond.), 421, 293–308.
Perin, M. S., Fried, V. A., Mignery, G. A., Jahn, R., and Südhof, T. C., (1990). Nature, 345, 260–263.
Pietrobon, D., (2002). Mol. Neurobiol. 25, 31–50.
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.
Pinto, A, Iwasa, K., Newland, C., Newsom-Davis, J., and Lang, B., (2002). Muscle Nerve, 25, 715–724.
Porter, R. R., and Reid, K. B., (1978). Nature, 275, 699–704.
Prior, C., Lang, B., Wray, D., and Newsom-Davis, J., (1985). Ann. Neurol. 17, 587–592.
Protti, D. A., Reisin, R., Mackinley, T. A., and Uchitel, O. D., (1996). Neurology, 46, 1391–1396.
Protti, D. A., and Uchitel, O. D., (1997). Pflügers Arch. 434, 406–412.
Pumplin, D. W., Reese, T. S., and Llinas, R., (1981). Proc. Natl. Acad. Sci. U.S.A. 78, 7210–7213.
Rammensee, H. G., Falk, K., and Rotzschke, O., (1993). Curr. Opin. Immunol. 5, 35–44.
Roberts, A., Perera, S., Lang, B., Vincent, A., and Newsom-Davis, J., (1985). Nature, 317, 737–739.
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.
Robitaille, R., Adler, E. M., and Charlton, M. P., (1990). Neuron, 5, 773–779.
Robitaille, R., and Charlton, M. P., (1992). J. Neurosci. 12, 297–305.
Robitaille, R., Garcia, M. L., Kaczorowski, G. J., and Charlton, M. P., (1993). Neuron, 11, 645–655.
Rosato-Siri, M. D., Piriz, J., Tropper, B. A., and Uchitel, O. D., (2002). Eur. J. Neurosci. 15, 1874–1880.
Rosato-Siri, M. D., and Uchitel, O. D., (1999). J. Physiol. (Lond.), 514, 533–540.
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.
Rosenfeld, M. R., Wong, E., Dalmau, J., Manley, G., Posner, J. B., Sher, E., Furneaux, H. M., (1993a). Ann. Neurol. 33, 113–120.
Rubenstein, A. E., Horowitz, S. H., and Bender, A. N., (1979). Neurology, 29, 720–723.
Sanders, D. B., (1994). Handbook of Myasthenia Gravis and Myasthenic Syndromes Marcell Dekker, New York, pp. 103–148.
Sanders, D. B., (1998). Ann. N. Y. Acad. Sci. 841, 811–816.
Sanders, D. B., Massey, J. M., Sanders, L. L., and Edwards, L. J., (2000). Neurology, 54, 603–607.
Sano, K., Enomoto, K., and Maeno, T., (1987). Eur. J. Pharmacol. 141, 235–241.
Santafe, M. M., Garcia, N., Lanuza, M. A., Uchitel, O. D., and Salon, I., Tomas J., (2002). Neuroscience, 110, 147–154.
Santafe, M. M., Garcia, N., Lanuza, M. A., Uchitel, O. D., and Tomas, J., (2001). Neuroscience, 102, 697–708.
Santafe, M. M., Urbano, F. J., Lanuza, M. A., Uchitel, O. D., (2000). Neuroscience, 95, 227–234.
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.
Sculptoreanu, A., Figourov, A., and De Groat, W. C., (1995). Am. J. Physiol. 269, C725–C732.
Sculptoreanu, A., Yoshimura, N., de Groat, W. C., and Somogyi, G. T., (2001). Neurochem. Res. 26, 933–942.
Sher, E., Carbone, E., and Clementi, F., (1993). Ann. N. Y. Acad. Sci. 681, 373–381.
Sher, E., Gotti, C., Canal, N., Scoppetta, C., Piccolo, G., Evoli, A., Clementi, F., (1989). Lancet, 2, 640–643.
Sher, E., Pandiella, A., and Clementi, F., (1990). Cancer Res. 50, 3892–3896.
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.
Silinsky, E. M., (1985). Pharmacol. Rev. 37, 81–132.
Singer, D., Biel, M., Lotan, I., Flockerzi, V., Hofmann, F., and Dascal, N., (1991). Science, 253, 1553–1557.
Smith, D. O., Conklin, M. W., Jensen, P. J., and Atchison, W. D., (1995). J. Physiol. (Lond.), 487, 115–123.
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.
Sugiura, Y., and Ko, C. P., (1997). J. Neurosci. 17, 1101–1111.
Takamori, M., Gutmann, L., Crosby, T. W., and Martin, J. D., (1972). Arch. Neurol. 26, 326–335.
Takamori, M., Hamada, T., Komai, K., Takahashi, M., and Yoshida, A., (1994). Ann. Neurol. 35, 74–80.
Takamori, M., Hamada, T., and Okumura, S., (1992). J. Neurol. Sci. 109, 182–187.
Takamori, M., Iwasa, K., and Komai, K., (1997). Neurology, 48, 1261–1265.
Takamori, M., Komai, K., and Iwasa, K., (2000a). Am. J. Med. Sci. 319, 204–208.
Takamori, M., Maruta, T., and Kamai, K., (2000b). Neurosci. Res. 36, 183–191.
Takamori, M., Okumura, S., Komai, K., and Satake, R., (1990). J. Neurol. Sci. 99, 219–227.
Takamori, M., Takahashi, M., Yasukawa, Y., Iwasa, K., Nemoto, Y., Suenaga, A., Nagataki, S., and Nakamura, T., (1995). J. Neurol. Sci. 133, 95–101.
Talley, E. M., Sadr, N. N., and Bayliss, D., (1997). J. Neurosci. 17, 4473–4485.
Tareilus, E., Schoch, J., and Breer, H., (1994). J. Neurochem. 62, 2283–2291.
Tsujihata, M., Kinoshita, I., Mori, M., Mori, K., Shirabe, S., Satoh, A., and Nagataki, S., (1987). J. Neurol. Sci. 81, 197–213.
Ueno, S., and Hara, Y., (1992). J. Neurol. Neurosurg. Psychia. 55, 409–410.
Urbano, F. J., Depetris, R. S., and Uchitel, O. D., (2001). Pflügers Arch. 441, 824–831.
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, 475–479
Viglione, M. P., O'Shaughnessy, T. J., and Kim, Y. I., (1995). J. Physicol. (Lond.), 488, 303–317.
Waterman, S. A., (1996). J. Neurosci. 16, 4155–4161.
Waterman, S. A., (1997). Br. J. Pharmacol. 120, 393–398.
Waterman, S. A., Lang, B., Newsom-Davis, J., (1997). Ann. Neurol. 42, 147–156.
Wessler, I., Dooley, D. J., Osswald, H., and Schlemmer, F., (1990). Neurosci. Lett. 108, 173–178.
Willcox, N., Demaine, A. G., Newsom-Davis, J., Welsh, K. I., Robb, S. A., and Spiro, S. G., (1985). Hum. Immunol. 14, 29–36.
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.
Wise, R. P., and MacDermot, V., (1962). J. Neurol. Neurosurg. Psychiatry, 25, 31–39.
Wisgirda, M. E., and Dryer, S. E., (1994). Proc. Natl. Acad. Sci. U.S.A. 91, 2858–2862.
Wray, D. W., Peers, C., Lang, B., Lande, S., and Newsom-Davis, J., (1987). Ann. N. Y. Acad. Sci. 505, 368–376.
Xu, Y. F., and Atchison, W. D., (1996). J. Pharmacol. Exp. Ther. 279, 1229–1236.
Xu, Y. F., Hewett, S. J., and Atchison, W. D., (1998). J. Neurophysiol. 80, 1056–1069.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Flink, M.T., Atchison, W.D. Ca2+ Channels as Targets of Neurological Disease: Lambert–Eaton Syndrome and Other Ca2+ Channelopathies. J Bioenerg Biomembr 35, 697–718 (2003). https://doi.org/10.1023/B:JOBB.0000008033.02320.10
Issue Date:
DOI: https://doi.org/10.1023/B:JOBB.0000008033.02320.10