Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 May 15;89(10):4628–4632. doi: 10.1073/pnas.89.10.4628

Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts.

N M Soldatov 1
PMCID: PMC49136  PMID: 1316612

Abstract

The nucleotide sequence of cDNA encoding the human fibroblast Ca2+ channel of L type (HFCC) has been determined. It is highly homologous to L-type channels previously cloned from rabbit lung and heart as well as from rat brain. At least four sites of molecular diversity were identified in the nucleotide sequence of HFCC. Three of these include regions encoding the transmembrane segments IIS6, IIIS2, and IVS3, which are known to be important for channel gating properties. The positions of these sites correlate with RNA splice sites, indicating that the molecular diversity of the transcripts is a result of alternative splicing. The fourth diversity region is located at the C-terminal region and comprises insertions and deletions. It is suggested that these variations may give rise to multiple subforms of HFCC with altered electrophysiological properties.

Full text

PDF
4628

Images in this article

4629Image
on p.4629
4632Image
on p.4632

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Biel M., Ruth P., Bosse E., Hullin R., Stühmer W., Flockerzi V., Hofmann F. Primary structure and functional expression of a high voltage activated calcium channel from rabbit lung. FEBS Lett. 1990 Sep 3;269(2):409–412. doi: 10.1016/0014-5793(90)81205-3. [DOI] [PubMed] [Google Scholar]
  2. Breitbart R. E., Andreadis A., Nadal-Ginard B. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annu Rev Biochem. 1987;56:467–495. doi: 10.1146/annurev.bi.56.070187.002343. [DOI] [PubMed] [Google Scholar]
  3. Dudkin S. M., Gnedoj S. N., Chernyuk N. N., Soldatov N. M. 1,4-Dihydropyridine receptor associated with Ca2+ channels in human embryonic fibroblasts. FEBS Lett. 1988 Jun 20;233(2):352–354. doi: 10.1016/0014-5793(88)80458-7. [DOI] [PubMed] [Google Scholar]
  4. Hui A., Ellinor P. T., Krizanova O., Wang J. J., Diebold R. J., Schwartz A. Molecular cloning of multiple subtypes of a novel rat brain isoform of the alpha 1 subunit of the voltage-dependent calcium channel. Neuron. 1991 Jul;7(1):35–44. doi: 10.1016/0896-6273(91)90072-8. [DOI] [PubMed] [Google Scholar]
  5. Jacob M., Gallinaro H. The 5' splice site: phylogenetic evolution and variable geometry of association with U1RNA. Nucleic Acids Res. 1989 Mar 25;17(6):2159–2180. doi: 10.1093/nar/17.6.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Koch W. J., Ellinor P. T., Schwartz A. cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta. Evidence for the existence of alternatively spliced forms. J Biol Chem. 1990 Oct 15;265(29):17786–17791. [PubMed] [Google Scholar]
  7. Koch W. J., Hui A., Shull G. E., Ellinor P., Schwartz A. Characterization of cDNA clones encoding two putative isoforms of the alpha 1 subunit of the dihydropyridine-sensitive voltage-dependent calcium channel isolated from rat brain and rat aorta. FEBS Lett. 1989 Jul 3;250(2):386–388. doi: 10.1016/0014-5793(89)80761-6. [DOI] [PubMed] [Google Scholar]
  8. McKenna E., Koch W. J., Slish D. F., Schwartz A. Toward an understanding of the dihydropyridine-sensitive calcium channel. Biochem Pharmacol. 1990 Apr 1;39(7):1145–1150. doi: 10.1016/0006-2952(90)90255-j. [DOI] [PubMed] [Google Scholar]
  9. Mikami A., Imoto K., Tanabe T., Niidome T., Mori Y., Takeshima H., Narumiya S., Numa S. Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel. Nature. 1989 Jul 20;340(6230):230–233. doi: 10.1038/340230a0. [DOI] [PubMed] [Google Scholar]
  10. Mori Y., Friedrich T., Kim M. S., Mikami A., Nakai J., Ruth P., Bosse E., Hofmann F., Flockerzi V., Furuichi T. Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature. 1991 Apr 4;350(6317):398–402. doi: 10.1038/350398a0. [DOI] [PubMed] [Google Scholar]
  11. Okayama H., Kawaichi M., Brownstein M., Lee F., Yokota T., Arai K. High-efficiency cloning of full-length cDNA; construction and screening of cDNA expression libraries for mammalian cells. Methods Enzymol. 1987;154:3–28. doi: 10.1016/0076-6879(87)54067-8. [DOI] [PubMed] [Google Scholar]
  12. Perez-Reyes E., Wei X. Y., Castellano A., Birnbaumer L. Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes. J Biol Chem. 1990 Nov 25;265(33):20430–20436. [PubMed] [Google Scholar]
  13. Rios E., Brum G. Involvement of dihydropyridine receptors in excitation-contraction coupling in skeletal muscle. Nature. 1987 Feb 19;325(6106):717–720. doi: 10.1038/325717a0. [DOI] [PubMed] [Google Scholar]
  14. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Snutch T. P., Leonard J. P., Gilbert M. M., Lester H. A., Davidson N. Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci U S A. 1990 May;87(9):3391–3395. doi: 10.1073/pnas.87.9.3391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Snutch T. P., Tomlinson W. J., Leonard J. P., Gilbert M. M. Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS. Neuron. 1991 Jul;7(1):45–57. doi: 10.1016/0896-6273(91)90073-9. [DOI] [PubMed] [Google Scholar]
  17. Starr T. V., Prystay W., Snutch T. P. Primary structure of a calcium channel that is highly expressed in the rat cerebellum. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5621–5625. doi: 10.1073/pnas.88.13.5621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tanabe T., Mikami A., Numa S., Beam K. G. Cardiac-type excitation-contraction coupling in dysgenic skeletal muscle injected with cardiac dihydropyridine receptor cDNA. Nature. 1990 Mar 29;344(6265):451–453. doi: 10.1038/344451a0. [DOI] [PubMed] [Google Scholar]
  19. Tanabe T., Takeshima H., Mikami A., Flockerzi V., Takahashi H., Kangawa K., Kojima M., Matsuo H., Hirose T., Numa S. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature. 1987 Jul 23;328(6128):313–318. doi: 10.1038/328313a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES