Immunological Properties Carcinoma Cell Lines: Pharmacological, Functional, and Voltage-operated Calcium Channels in Small Cell Lung

Different subtypes of voltage-operated calcium channels (VOCCs) are expressed in different tissues and can be distinguished by functional and pharmacological criteria. One type of high voltage-activated calcium channel, specifically recognized by the peptide neurotoxin u-conotoxin (wCTx), is expressed only in neurons. Seven different human small cell lung carcinoma (SCC) cell lines were also found to bind 125I-o>CTx. The binding was specific, saturable, and of high affinity. "5I-wCTx binding was not antagonized by the calcium channel ligands verapamil, nitrendipine, and diltiazem. There was a correlation between the amount of toxin binding and the detection of depolarization-induced calcium fluxes studied with the fluorimetrie probe Fura2. Fura2 experi ments also demonstrated that, in addition to wCTx-sensitive calcium channels, SCC cell lines also expressed wCTx-insensitive calcium chan nels, which were antagonized by nitrendipine and verapamil. '"I-uCTx-labeled VOCCs from SCC cells were, furthermore, precip itated by anti-VOCC autoantibodies obtained from patients affected by the Lambert-Eaton myasthénie syndrome, a neuromuscular disease often associated with SCC. The present findings further indicate the presence of neuronal molecules with important biological function on SCC plasma membrane and add new insights into the pathogenetic mechanism of autoimmune neurological paraneoplastic diseases, like Lambert-Eaton myasthénie syndrome.