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.