Molecular Diversity of Neuronal-Type Calcium Channels Identified in Small Cell Lung Carcinoma

MIEKO OGURO-OKANO, GUY E. GRIESMANN, ERIC D. WIEBEN, SARAH J. SLAYMAKER, TERRY P. SNUTCH, VANDA A. LENNON

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Using the polymerase chain reaction (PCR), we identified RNA transcripts for two distinct classes of neuronal-type voltage-gated Ca2+ channels (VGCC) in a prototypic small cell lung carcinoma (SCLC) cell line, SCC-9. Oligonucleotide primers were designed to encode amino acid sequences common to α1-subunits of known neuronal VGCC classes. Sequencing of complementary DNA (cDNA) clones derived from two independent PCR products revealed that one corresponded to a brain class A VGCC fragment predicted to encode a P-type VGCC (insensitive to dihydropyridines and ω-conotoxin) characteristic of cerebellar Purkinje cells but not previously identified in humans. The second PCR product was identical (except for one conservative nucleotide difference) to a fragment of the class D VGCC of neurons and neuroendocrine cells, which encodes an L-type VGCC (sensitive to dihydropyridines). By Northern blot analyses, both cDNAs hybridized to messenger RNAs (mRNAs) obtained from SCC-9; class D hybridized additionally to human cerebral cortical mRNA, but neither hybridized to mRNA from the skeletal muscle cell line TE671. Although no cDNA corresponding to class B VGCC (N-type) was identified, SCLCs are known to express VGCC that are sensitive to ω-conotoxin and coprecipitate with 125I-labeled-ω-conotoxin when complexed with serum IgG from patients with the Lambert-Eaton myasthenic syndrome. The multiple classes of neuronal-type VGCC expressed in SCLC could conceivably have both unique and related antigenic determinants that may give rise to antineuronal autoimmune responses. This would account for a spectrum of paraneoplastic neurologic disorders including the Lambert-Eaton syndrome and subacute cerebellar degeneration.

Original languageEnglish (US)
Pages (from-to)1150-1159
Number of pages10
JournalMayo Clinic proceedings
Volume67
Issue number12
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Medicine(all)

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