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. 1990 Feb;421:293–308. doi: 10.1113/jphysiol.1990.sp017945

Selective action of myasthenic syndrome antibodies on calcium channels in a rodent neuroblastoma x glioma cell line.

C Peers 1, B Lang 1, J Newsom-Davis 1, D W Wray 1
PMCID: PMC1190085  PMID: 2161458

Abstract

1. The effect of Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) on Ca2+ channels in undifferentiated mouse neuroblastoma x rat glioma hybrid cells (NG 108 15) was studied using the whole-cell patch clamp technique. 2. Sustained inward Ca2+ channel currents were evoked by depolarizing pulses from holding potentials of -80 and -40 mV, and were blocked by 5 microM-nitrendipine (L-type currents). Transient inward Ca2+ channel currents were activated from a holding potential of -80 mV by small depolarizing steps (T-type currents). Noradrenaline (10 microM) was without effect on transient currents. 3. LEMS IgG selectively reduced sustained (L-type) Ca2+ channel current amplitudes evoked from either holding potential used. In the presence of nitrendipine (5 microM), there was no significant effect of LEMS IgG on the remaining transient (T-type) Ca2+ channel current amplitudes. 4. Studies of the potential for maximal inward current indicated that voltage sensitivities of both L- and T-type Ca2+ channel current amplitudes were unaffected by LEMS IgG, whether recorded in the presence or absence of nitrendipine. LEMS IgG had no significant effect on the time-to-peak or decay of Ca2+ channel currents. 5. It is concluded that LEMS IgG acts selectively to cause functional loss of L-type, but not T-type, Ca2+ channels in NG 108 15 cells. Any effect of LEMS IgG on N-type channels (not present in these undifferentiated cells) was not studied here. LEMS IgG also acts at motor nerve terminal Ca2+ channels leading to muscle weakness. Thus antigenic similarities must exist between L-type channels in NG 108 15 cells and Ca2+ channels at motor nerve terminals.

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Selected References

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  1. Bregestovski P. D., Miledi R., Parker I. Blocking of frog endplate channels by the organic calcium antagonist D600. Proc R Soc Lond B Biol Sci. 1980 Dec 31;211(1182):15–24. doi: 10.1098/rspb.1980.0155. [DOI] [PubMed] [Google Scholar]
  2. Docherty R. J. Gadolinium selectively blocks a component of calcium current in rodent neuroblastoma x glioma hybrid (NG108-15) cells. J Physiol. 1988 Apr;398:33–47. doi: 10.1113/jphysiol.1988.sp017027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Docherty R. J., McFadzean I. Noradrenaline-Induced Inhibition of Voltage-Sensitive Calcium Currents in NG108-15 Hybrid Cells. Eur J Neurosci. 1989 Mar;1(2):132–140. doi: 10.1111/j.1460-9568.1989.tb00780.x. [DOI] [PubMed] [Google Scholar]
  4. Engel A. G., Fukuoka T., Lang B., Newsom-Davis J., Vincent A., Wray D. Lambert-Eaton myasthenic syndrome IgG: early morphologic effects and immunolocalization at the motor endplate. Ann N Y Acad Sci. 1987;505:333–345. doi: 10.1111/j.1749-6632.1987.tb51302.x. [DOI] [PubMed] [Google Scholar]
  5. Fox A. P., Nowycky M. C., Tsien R. W. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol. 1987 Dec;394:149–172. doi: 10.1113/jphysiol.1987.sp016864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fox A. P., Nowycky M. C., Tsien R. W. Single-channel recordings of three types of calcium channels in chick sensory neurones. J Physiol. 1987 Dec;394:173–200. doi: 10.1113/jphysiol.1987.sp016865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fukunaga H., Engel A. G., Lang B., Newsom-Davis J., Vincent A. Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7636–7640. doi: 10.1073/pnas.80.24.7636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fukuoka T., Engel A. G., Lang B., Newsom-Davis J., Prior C., Wray D. W. Lambert-Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones. Ann Neurol. 1987 Aug;22(2):193–199. doi: 10.1002/ana.410220203. [DOI] [PubMed] [Google Scholar]
  9. Gotgil'f N. M., Magazanik L. G. Vliianie blokatorov kal'tsievykh kanalov (verapamil, D-600 i iony margantsa) na osvobozhdenie mediatora iz dvigatel'nykh nervnykh okonchanii v myshtse liagushki. Neirofiziologiia. 1977;9(4):415–422. [PubMed] [Google Scholar]
  10. HOREJSI J., SMETANA R. The isolation of gamma globulin from blood-serum by rivanol. Acta Med Scand. 1956 Jun 30;155(1):65–70. doi: 10.1111/j.0954-6820.1956.tb14351.x. [DOI] [PubMed] [Google Scholar]
  11. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  12. Kim Y. I., Neher E. IgG from patients with Lambert-Eaton syndrome blocks voltage-dependent calcium channels. Science. 1988 Jan 22;239(4838):405–408. doi: 10.1126/science.2447652. [DOI] [PubMed] [Google Scholar]
  13. Lambert E. H., Elmqvist D. Quantal components of end-plate potentials in the myasthenic syndrome. Ann N Y Acad Sci. 1971 Sep 15;183:183–199. doi: 10.1111/j.1749-6632.1971.tb30750.x. [DOI] [PubMed] [Google Scholar]
  14. Lang B., Newsom-Davis J., Peers C., Prior C., Wray D. W. The effect of myasthenic syndrome antibody on presynaptic calcium channels in the mouse. J Physiol. 1987 Sep;390:257–270. doi: 10.1113/jphysiol.1987.sp016698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lang B., Newsom-Davis J., Prior C., Wray D. Antibodies to motor nerve terminals: an electrophysiological study of a human myasthenic syndrome transferred to mouse. J Physiol. 1983 Nov;344:335–345. doi: 10.1113/jphysiol.1983.sp014943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lang B., Newsom-Davis J., Wray D. W. The effect of Lambert-Eaton myasthenic syndrome antibody on slow action potentials in mouse cardiac ventricle. Proc R Soc Lond B Biol Sci. 1988 Oct 22;235(1278):103–110. doi: 10.1098/rspb.1988.0065. [DOI] [PubMed] [Google Scholar]
  17. Lang B., Newsom-Davis J., Wray D., Vincent A., Murray N. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet. 1981 Aug 1;2(8240):224–226. doi: 10.1016/s0140-6736(81)90474-8. [DOI] [PubMed] [Google Scholar]
  18. Nachshen D. A., Blaustein M. P. The effects of some organic "calcium antagonists" on calcium influx in presynaptic nerve terminals. Mol Pharmacol. 1979 Sep;16(2):576–586. [PubMed] [Google Scholar]
  19. Narahashi T., Tsunoo A., Yoshii M. Characterization of two types of calcium channels in mouse neuroblastoma cells. J Physiol. 1987 Feb;383:231–249. doi: 10.1113/jphysiol.1987.sp016406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
  21. O'Neill J. H., Murray N. M., Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain. 1988 Jun;111(Pt 3):577–596. doi: 10.1093/brain/111.3.577. [DOI] [PubMed] [Google Scholar]
  22. Prior C., Lang B., Wray D., Newsom-Davis J. Action of Lambert-Eaton myasthenic syndrome IgG at mouse motor nerve terminals. Ann Neurol. 1985 Jun;17(6):587–592. doi: 10.1002/ana.410170610. [DOI] [PubMed] [Google Scholar]
  23. Roberts A., Perera S., Lang B., Vincent A., Newsom-Davis J. Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line. Nature. 1985 Oct 24;317(6039):737–739. doi: 10.1038/317737a0. [DOI] [PubMed] [Google Scholar]
  24. Tsien R. W., Lipscombe D., Madison D. V., Bley K. R., Fox A. P. Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci. 1988 Oct;11(10):431–438. doi: 10.1016/0166-2236(88)90194-4. [DOI] [PubMed] [Google Scholar]

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