Invited Review
Neuromuscular disease and calcium channels
David A. Greenberg MD, PhD,
Corresponding Author
David A. Greenberg MD, PhD
Buck Center for Research in Aging, Novato, California, USA and Department of Neurology, University of California, San Francisco, San Francisco, California, USA
Buck Center for Research in Aging, PO Box 638, Novato, CA 94948-0638Search for more papers by this authorDavid A. Greenberg MD, PhD,
Corresponding Author
David A. Greenberg MD, PhD
Buck Center for Research in Aging, Novato, California, USA and Department of Neurology, University of California, San Francisco, San Francisco, California, USA
Buck Center for Research in Aging, PO Box 638, Novato, CA 94948-0638Search for more papers by this authorFirst published: 15 September 1999
Citations: 14
Abstract
Calcium channels that are regulated by voltage have an important role in linking cellular stimulation to physiological responses in the nervous system. In addition, a number of autoimmune or genetic disorders that affect calcium channels (channelopathies) have been identified, including several that affect neuromuscular function. These include the Lambert–Eaton myasthenic syndrome, which is associated with autoantibodies directed against neuronal calcium channels, as well as at least two inherited neuromuscular diseases—hypokalemic periodic paralysis and some varieties of malignant hyperthermia—that affect calcium channels in skeletal muscle. Preliminary progress has been achieved in understanding the relationship between these immunological or genetic abnormalities and the alterations in channel function that they produce. A major challenge that remains is to determine how calcium channelopathies lead to the curious assortment of paroxysmal and progressive disorders that are observed clinically. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1341–1349, 1999
REFERENCES
- 1Berridge MJ. Neuronal calcium signaling. Neuron 1998; 21: 13–26. Medline
- 2Berridge MJ, Bootman MD, Lipp P. Calcium—a life and death signal. Nature 1998; 395: 645–648. Medline
- 3Boerman RH, Ophoff RA, Links TP, van Eijk R, Sandkuijl LA, Elbaz A, Vale-Santos JE, Wintzen AR, van Deutekom J, Isles DE, Fontaine B, Padberg GW, Frants RR. Mutation in DHP receptor alpha-1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis. J Med Genet 1995; 32: 44–47. Medline
- 4Britt BA. Malignant hyperthermia. In: RJM Lane, editor. Handbook of muscle disease. New York: Marcel Dekker; 1996. p 451–471.
- 5Burgess DL, Jones JM, Meisler MH, Noebels JL. Mutation of the Ca2+ channel β subunit gene Cchb4 is associated with ataxia and seizures in lethargic (lh) mouse. Cell 1997; 88: 385–392. Medline
- 6Chuang RS-I, Jaffe H, Cribbs L, Perez-Reyes E, Swartz KJ. Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nat Neurosci 1998; 1: 668–674. Medline
- 7Elbaz A, Vale-Santos J, Jurkat-Rott K, Lapie P, Ophoff RA, Bady B, Links TP, Piussan C, Vila A, Monnier N, Padberg GW, Abe K, Feingold N, Guimaraes J, Wintzen AR, van der Hoeven JH, Saudubray JM, Grunfeld JP, Lenoir G, Nivet H, Echenne B, Frants RR, Fardeau M, Lehmann-Horn F, Fontaine B. Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 Caucasian families. Am J Hum Genet 1995; 56: 374–380. Medline
- 8Ellerby LM, Hackam AS, Propp SS, Ellerby HM, Rabizadeh S, Cashman NR, Trifiro MA, Pinsky L, Wellington CL, Salvesen GS, Hayden MR, Bredesen DE. Kennedy's disease: caspase cleavage of the androgen receptor is a crucial event in cytotoxicity. J Neurochem 1999; 72: 185–195. Medline
- 9Ertel SI, Ertel EA. Low-voltage-activated T-type Ca2+; channels. Trends Pharmacol Sci 1997; 18: 37–42. Medline
- 10Fletcher CF, Lutz CM, O'Sullivan CM, Shaughnessy JD Jr, Hawkes R, Frankel WN, Copeland NG, Jenkins NA. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 1996; 87: 607–617. Medline
- 11Fujii J, Otsu K, Zorzato F, de Leon S, Khanna VK, Weiler JE, O'Brien PJ, MacLennan DH. Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 1991; 253: 448–451. Medline
- 12Fukunaga H, Engel AG, Lang B, Newsom-Davis J, Vincent A. Passive transfer of Lambert–Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic mmebrane active zones. Proc Natl Acad Sci USA 1983; 80: 7636–7640. Medline
- 13Greenberg DA. Calcium channels in neurological disease. Ann Neurol 1997; 42: 275–282. Medline
- 14Hans M, Luvisetto S, Williams ME, Spagnolo M, Urrutia A, Tottene A, Brust PF, Johnson EC, Harpold MM, Stauderman KA, Pietrobon D. Functional consequneces of mutations in the human α1A calcium channel subunit linked to familial hemiplegic migraine. J Neurosci 1999; 19: 1610–1619. Medline
- 15Iles DE, Lehmann-Horn F, Scherer SW, Tsui L-C, Weghuis DO, Suijkerbuijk RF, Heytens L, Mikala G, Schwartz A, Ellis FR, Stewart AD, Deufel T, Wieringa B. Localization of the gene encoding the α2/δ-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. Hum Mol Genet 1994; 3: 969–975. Medline
- 16Jurkat-Rott K, Lehmann-Horn F, Elbaz A, Heine R, Gregg RG, Hogan K, Powers PA, Lapie P, Vale-Santos JE, Weissenbach J, Fontaine B. A calcium channel mutation causing hypokalemic periodic paralysis. Hum Molec Genet 1994; 3: 1415–1419. Medline
- 17Lang B, Newsom-Davis J, Wray D, Vincent A. Autoimmune aetiology for myasthenic (Eaton–Lambert) syndrome. Lancet 1981; 2: 224–226. Medline
- 18Lennon VA, Kryzer TJ, Griesmann GE, O'Suilleabhain PE, Windebank AJ, Woppmann A, Miljanich GP, Lambert EH. Calcium-channel antibodies in the Lambert–Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 1995; 332: 1467–1474. Medline
- 19Letts VA, Felix R, Biddlecome GH, Arikkath J, Mahaffey CL, Valenzuela A, Bartlett FSI, Mori Y, Campbell KP, Frankel WN. The mouse stargazer gene encodes a neuronal Ca2+-channel γ subunit. Nat Genet 1998; 19: 340–347. Medline
- 20MacLennan DH. Discordance between phenotype and genotype in malignant hyperthermia. Curr Opin Neurol 1995; 8: 397–401. Medline
- 21MacLennan DH, Phillips MS. Malignant hyperthermia. Science 1992; 256: 789–794. Medline
- 22Meir A, Dolphin AC. Known calcium channel α1 subunits can form low threshold small conductance channels with similarities to native T-type channels. Neuron 1998; 20: 341–351. Medline
- 23Meriney SD, Hulsizer SC, Lennon VA, Grinnell AD. Lambert–Eaton myasthenic syndrome immunoglobulins react with multiple types of calcium channels in small-cell lung carcinoma. Ann Neurol 1996; 40: 739–749. Medline
- 24Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME. P-type calcium channels blocked by the spider toxin ω-Aga-IVA. Nature 1992; 355: 827–829. Medline
- 25Monnier N, Procaccio V, Stieglitz P, Lunardi J. Malignant-hyperthermia susceptibility is associated with a mutation of the alpha-1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium channel receptor in skeletal muscle. Am J Hum Genet 1997; 60: 1316–1325. Medline
- 26Morrill JA, Brown RHJ, Cannon SC. Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528H. J Neurosci 1998; 18: 10320–10334. Medline
- 27Moslehi R, Langlois S, Yam I, Friedman JM. Linkage of malignant hyperthermia and hyperkalemic periodic paralysis to the adult skeletal muscle sodium channel (SCN4A) gene in a large pedigree. Am J Med Genet 1998; 76: 21–27.
Medline
10.1002/(SICI)1096-8628(19980226)76:1<21::AID-AJMG3>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 28Newcomb R, Szoke B, Palma A, Wang G, Chen X, Hopkins W, Cong R, Miller J, Urge L, Tarczy-Hornoch K, Loo JA, Dooley DJ, Nadasdi L, Tsien RW, Lemos J, Miljanicj G. Selective peptide antagonist of the class E calcium channel from the venom of Hysterocrates gigas. Biochemistry 1998; 37: 15353–15362. Medline
- 29Nooney JM, Lambert RC, Feltz A. Identifying neuronal non-L Ca2+ channels—more than stamp collecting? Trends Pharmacol Sci 1997; 18: 363–371. Medline
- 30O'Neill JH, Murray NMF, Newsom-Davis J. The Lambert–Eaton myasthenic syndrome: a review of 50 cases. Brain 1988; 111: 577–596. Medline
- 31O'Suilleabhain P, Low PA, Lennon VA. Autonomic dysfunction in the Lambert–Eaton myasthenic syndrome: serologic and clinical correlates. Neurology 1998; 50: 88–93. Medline
- 32Olivera BM, Rivier J, Clark C, Ramilo CA, Corpuz GP, Abogadie FC, Mena E, Woodwrad SR, Hillyard DR, Cruz LJ. Diversity of Conus neuropeptides. Science 1990; 249: 257–263. Medline
- 33Pinto A, Gillard S, Moss F, Whyte K, Brust P, Williams M, Stauderman K, Harpold M, Lang B, Newsom-David J, Bleakman D, Lodge D, Boot J. Human autoantibodies specific for the α1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurons. Proc Natl Acad Sci USA 1998; 95: 8328–8333. Medline
- 34Plassart E, Elbaz A, Santos JV, Reboul J, Lapie P, Chauveau D, Jurkat-Rott K, Guimaraes J, Saudubray J-M, Weissenbach J, Lehmann-Horn F, Fontaine B. Genetic heterogeneity in hypokalemic periodic paralysis (hypoPP). Hum Genet 1994; 94: 551–556. Medline
- 35Ptacek LJ, Tawil R, Griggs RC, Engel AG, Layzer RB, Kwiecinski H, McManis PG, Santiago L, Moore M, Fouad G, Bradley P, Leppert MF. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 1994; 77: 863–868. Medline
- 36Stanley EF. The calcium channel and the organization of the presynaptic transmitter release face. Trends Neurosci 1997; 20: 404–409. Medline
- 37Striessnig J, Grabner M, Mitterdorfer J, Hering S, Sinnegger MJ, Glossman H. Structural basis of drug binding to L Ca2+ channels. Trends Pharmacol Sci 1998; 19: 108–115. Medline
- 38Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 1987; 328: 313–318. Medline
- 39Tawil R, Griggs RC. Hypokalemic periodic paralysis. In: RJM Lane, editor. Handbook of muscle disease. New York: Marcel Dekker; 1996 p 329–337.
- 40Verkhratsky A, Toescu EC. Calcium and neuronal ageing. Trends Neurosci 1998; 21: 2–7. Medline
- 41Voltz R, Carpentier AF, Rosenfeld MR, Posner JB, Dalmau J. P/Q-type voltage-gated calcium channel antibodies in paraneoplastic disorders of the central nervous system. Muscle Nerve 1999; 22: 119–122.
Medline
10.1002/(SICI)1097-4598(199901)22:1<119::AID-MUS19>3.0.CO;2-5 CAS PubMed Web of Science® Google Scholar
- 42Walker D, De Waard M. Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function. Trends Neurosci 1998; 21: 148–154. Medline
- 43Wellington CL, Ellerby LM, Hackam AS, Margolis L, Trifiro MA, Singaraja R, McCutcheon K, Salvesen GS, Propp SS, Bromm M, Rowland KJ, Zhang T, Rasper D, Roy S, Thornberry N, Pinsky L, Kakizuka A, Ross CA, Nicholson DW, Bredesen DE, Hayden MR. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem 1998; 273: 9158–9167. Medline
- 44Wu L-G, Borst JGJ, Sakmann B. R-type Ca2+ currents evoke transmitter release at a rat central synapse. Proc Natl Acad Sci USA 1998; 95: 4720–4725. Medline
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