ALPHA(1) AND ALPHA(2) CA2+ CHANNEL SUBUNIT EXPRESSION IN HUMAN NEURONAL AND SMALL-CELL CARCINOMA-CELLS

Monoclonal antibodies that recognize skeletal muscle dihydropyridine-sensitive calcium channel subunits were used to identify similar proteins in neuronal and small cell carcinoma cell lines. alpha(1)-related proteins were detected by FACS analysis on the surface of human neuroblastoma (IMR 32) and small cell carcinoma (DMS 273 and DMS 114) cell lines. alpha(1)-like polypeptides from these cells were isolated and partially characterized. The polypeptides exhibit an M(r) similar to that of the L-type channel alpha(1) subunit and are recognized by two distinct anti-alpha(1) mAbs. The data provide biochemical evidence for structural similarities between the alpha(1) subunit of small cell carcinoma and neuronal cell lines. Similarly, an alpha(2)-like protein was characterized from these cells. Because alpha(2) is a subunit shared by many subtypes of calcium channels, these data suggest that subunits other than the pore-forming alpha(1) subunit may play an important role in etiology of Lambert-Eaton syndrome. We demonstrate directly that small cell carcinoma and a cell line derived from peripheral neurons share L-type calcium channel-related proteins and a protein common to many voltage-gated calcium channel subtypes. These data support a model that proposes that cross-reactivity of anti-tumor cell antibodies with presynaptic elements, possibly calcium channels, plays a role in the development of Lambert-Eaton syndrome.