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

• Published in: The Journal of physiology 1990-02, Vol.421 (1), p.293-308
• Main Authors: Peers, C, Lang, B, Newsom‐Davis, J, Wray, D W
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Antibodies, Neoplasm - immunology; Biological and medical sciences; Calcium Channels - physiology; Cell Line; Glioma - physiopathology; Humans; Immunoglobulin G - immunology; Lambert-Eaton Myasthenic Syndrome - immunology; Medical sciences; Mice; Neuroblastoma - physiopathology; Neurology; Nitrendipine - pharmacology; Norepinephrine - pharmacology; Rodentia; Tumor Cells, Cultured - physiology; Tumors of the nervous system. Phacomatoses
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1990.sp017945

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.