Down‐regulation of non‐L‐, non‐N‐type (Q‐like) Ca2+ channels by Lambert‐Eaton myasthenic syndrome (LEMS) antibodies in rat insulinoma RINm5F cells

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Abstract
The action exerted on non‐L‐, non‐N‐type (Q‐like) Ca2+ 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 Ca 2+ channels. In agreement with previous observations, LEMS IgGs also reduced by 20–33% the dihydropyridine‐sensitive (L‐type) Bat+ 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 PIQ‐type Ca2+ channels controlling acetylcholine release from mammalian neuromuscular junctions.