Lambert-Eaton myasthenic syndrome immunoglobulins react with multiple types of calcium channels in small-cell lung carcinoma

Abstract

Barium currents through voltage-gated calcium (Ca2+) channels were studied in the small-cell lung carcinoma cell line NCI-H345 using patch clamp techniques. Pharmacological dissection of whole-cell barium currents revealed that 23% of the current was sensitive to nitrendipine, 35% to omega-conotoxin GVIA, and between 10 and 39% to omega-Aga-IVA. This implies that these cells express L-, N-, and P-type calcium channels. Only large cells expressed current that was sensitive to omega-Aga-IVA. The size dependency of this P-type channel expression may reflect the cell cycle stage. Cell-attached recordings revealed three unitary conductances: 5 to 6 pS, 10 to 12 pS, and 20 to 23 pS. The largest conductance channel (20-23 pS) was sensitive to Bay K 8644 and is presumed to represent L-type calcium channels. The frequency of observing the medium conductance channel (10-12 pS) was reduced by exposure to omega-conotoxin GVIA and may represent N-type channels. Incubation of cells with Lambert-Eaton myasthenic syndrome IgG for 24 to 48 hours removed up to 71% of the whole-cell current. Incubation with control human IgG (normal or myasthenia gravis) had no effect. Lambert-Eaton myasthenic syndrome IgG did not selectively target one "presynaptic" type of calcium channel, but rather appeared to target many of the calcium channel types that are expressed on small-cell lung carcinoma cells.