Down-regulation of non-L-, non-N-type (Q-like) Ca2+ channels by Lambert-Eaton myasthenic syndrome (LEMS) antibodies in rat insulinoma RINm5F cells.
The action exerted on non-L-, non-N-type (Q-like) Ca 2+ channels by immunoglobulins G (IgGs) obtained from two patients with Lambert-Eaton myasthenic syndrome (LEMS) was investigated in the rat insulinoma RINm5F cell line. LEMS IgGs reduced by 30-36% the whole-cell Ba2+ currents through Q-like Ca2+ channels at +10 mV without significantly modifying their voltage dependence and activation kinetics. Single- and multiple-channel recordings in cell-attached and outside-out patches of cells treated with LEMS IgGs showed no significant changes of the channel elementary properties but rather a decreased number of active channels per patch. This suggests that Q-like current depression by LEMS autoantibodies is mostly due to a down-regulation of functioning Ca2+ channels. In agreement with previous observations, LEMS IgGs also reduced by 20-33% the dihydropyridine-sensitive (L-type) Ba2+ current. The suggested down-regulation of Q-like channels by LEMS IgGs in RINm5F cells may have a functional correlation with the depressive action of LEMS autoantibodies on the P/Q-type Ca2+ channels controlling acetylcholine release from mammalian neuromuscular junctions.
Magnelli
V
V
Department of Neuroscience, Corso Raffaello 30, Turin, Italy.
Grassi
C
C
Parlatore
E
E
Sher
E
E
Carbone
E
E
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007340:Insulinoma; D015640:Ion Channel Gating; D015624:Lambert-Eaton Myasthenic Syndrome / Q000276:immunology* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured; D020866:omega-Conotoxin GVIA
D001323:Autoantibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007074:Immunoglobulin G; D010455:Peptides; D020866:omega-Conotoxin GVIA; D009543:Nifedipine