Molecular diversity of neuronal-type calcium channels identified in small cell lung carcinoma

M. Oguro-Okano, G. E. Griesmann, Eric D Wieben, S. J. Slaymaker, T. P. Snutch, Vanda A Lennon

Research output: Contribution to journalArticle

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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
StatePublished - 1992

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Conotoxins
Small Cell Lung Carcinoma
Calcium Channels
Lambert-Eaton Myasthenic Syndrome
Dihydropyridines
Complementary DNA
Polymerase Chain Reaction
Messenger RNA
Cell Line
Neuroendocrine Cells
DNA Primers
Purkinje Cells
Nervous System Diseases
Autoimmunity
Northern Blotting
Muscle Cells
Epitopes
Amino Acid Sequence
Skeletal Muscle
Nucleotides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Molecular diversity of neuronal-type calcium channels identified in small cell lung carcinoma. / Oguro-Okano, M.; Griesmann, G. E.; Wieben, Eric D; Slaymaker, S. J.; Snutch, T. P.; Lennon, Vanda A.

In: Mayo Clinic Proceedings, Vol. 67, No. 12, 1992, p. 1150-1159.

Research output: Contribution to journalArticle

Oguro-Okano, M, Griesmann, GE, Wieben, ED, Slaymaker, SJ, Snutch, TP & Lennon, VA 1992, 'Molecular diversity of neuronal-type calcium channels identified in small cell lung carcinoma', Mayo Clinic Proceedings, vol. 67, no. 12, pp. 1150-1159.
Oguro-Okano, M. ; Griesmann, G. E. ; Wieben, Eric D ; Slaymaker, S. J. ; Snutch, T. P. ; Lennon, Vanda A. / Molecular diversity of neuronal-type calcium channels identified in small cell lung carcinoma. In: Mayo Clinic Proceedings. 1992 ; Vol. 67, No. 12. pp. 1150-1159.
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