Inhibition of low- and high-threshold Ca2+ channels of human neuroblastoma IMR32 cells by Lambert-Eaton myasthenic syndrome (LEMS) IgGs.
IgGs from two LEMS patients applied to human neuroblastoma IMR32 cells reduced the density of low- (LVA; T) and high-threshold (HVA; L and N) Ba2+ currents by different percentages: 36% (LVA) and 56% (HVA) for one and 48% and 45% for the other. A pharmacological assay of IgGs action based on the block of L-type channel by nifedipine and on the delayed activation of N-type channel by noradrenaline, indicated a preferential inhibition of the N-type current in IMR32 cells (55% and 47% for the two patients). The L-type current, contributing to approximately one-third of the total, was also depressed by LEMS IgGs but to a minor degree (49% and 30%). Except for an increase of single N-type channel inactivation, LEMS antibodies preserved the elementary properties of single HVA channels, suggesting that the macroscopic current reduction after IgGs treatment is likely due to a decrease in the number of active HVA Ca2+ channels.
Grassi
C
C
Institute of Human Physiology, UCSC, Rome, Italy.
Magnelli
V
V
Carabelli
V
V
Sher
E
E
Carbone
E
E
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004056:Differential Threshold; D004553:Electric Conductivity; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D015624:Lambert-Eaton Myasthenic Syndrome / Q000097:blood*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007074:Immunoglobulin G; D009543:Nifedipine; D009638:Norepinephrine