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 ω‐conotoxin GVIA, and between 10 and 39% to ω‐Aga‐IVA. This implies that these cells express L‐, N‐, and P‐type calcium channels. Only large cells expressed current that was sensitive to ω‐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 ω‐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 maysthenic 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.