Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 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.

Full text

PDF
304

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES