The action of Lambert–Eaton myasthenic syndrome immunoglobulin G on cloned human voltage‐gated calcium channels

Abstract

In the Lambert–Eaton myasthenic syndrome (LEMS), immunoglobulin G (IgG) autoantibodies to presynaptic voltage‐gated calcium channels (VGCCs) at the neuromuscular junction lead to a reduction in nerve‐evoked release of neurotransmitter and muscle weakness. We have examined the action of LEMS IgGs on cloned human VGCCs stably expressed in transfected human embryonic kidney (HEK293) cell lines: 10–13 (α_1A‐2, α_2bδ, β_4a) and C2D7 (α_1B‐1 , α_2bδ, β_1b). All LEMS IgGs studied showed surface binding to [¹²⁵I]‐ω‐CTx‐MVIIC‐labeled VGCCs in the α_1A cell line and two of six IgGs showed surface binding to [¹²⁵I]‐ω‐CTx‐GVIA‐labeled VGCCs in the α_1B cell line. We next studied the effect of LEMS IgGs (2 mg/ml) on whole‐cell calcium currents in the α_1A and α_1B cell lines. Overnight treatment of α_1A (10–13) cells with LEMS IgGs led to a significant reduction in peak current density without alteration of the current–voltage relationship or the voltage dependence of steady‐state inactivation. In contrast, LEMS IgGs did not reduce peak current density in the α_1B cell line. Overall these data demonstrate the specificity of LEMS IgGs for the α_1A cell line and suggest that LEMS IgGs bind to and downregulate VGCCs in this cell line. Although several LEMS IgGs can be shown to bind to the α_1B (C2D7) cell line, no functional effects were seen on this channel. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002