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

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.