Selective action of myasthenic syndrome antibodies on calcium channels in a rodent neuroblastoma x glioma cell line.
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.
Peers
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C
Department of Pharmacology, Royal Free Hospital Medical School, London.
Lang
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B
Newsom-Davis
J
J
Wray
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DW
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D005910:Glioma / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D015624:Lambert-Eaton Myasthenic Syndrome / Q000276:immunology*; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000502:physiology
D000912:Antibodies, Neoplasm; D015220:Calcium Channels; D007074:Immunoglobulin G; D009568:Nitrendipine; D009638:Norepinephrine