Home LiteratureArticle Details
PMID: 1317577 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular cloning of an atypical voltage-gated sodium channel expressed in human heart and uterus: evidence for a distinct gene family.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 11 ·1992-06-01 ·Pages 4893-7

George AL, Knittle TJ, Tamkun MM

Abstract

Previously cloned voltage-dependent sodium channels exhibit a high degree of homology to one another and appear to comprise a single multigene family. We have now isolated and characterized cDNAs from both human adult heart and fetal skeletal muscle that encode a sodium channel alpha subunit that exhibits only moderate primary structure identity with other sodium channels and is prominently expressed in both heart and uterus. The approximately 7.2-kilobase cDNA sequence, designated hNav2.1, predicts a 1682-amino acid protein that bears 52%, 49%, and 46% overall identity with sodium channels cloned from rat brain, skeletal muscle, and heart, respectively. Positively charged S4 segments are present in hNav2.1, but there are fewer basic residues in repeat domains 1, 3, and 4 than in other cloned sodium channels. The cloning of hNav2.1 provides evidence for greater evolutionary divergence among voltage-dependent sodium channels and suggests that other sodium channel gene subfamilies may exist. The unique amino acid sequences in regions known to be involved in voltage-dependent activation and inactivation suggest that hNav2.1 will have novel gating properties.

MeSH Terms
Amino Acid Sequence Cloning, Molecular DNA/genetics Female Gene Expression Heart/physiology Humans Ion Channel Gating Membrane Potentials Molecular Sequence Data Multigene Family RNA, Messenger/genetics Sequence Alignment Sodium Channels/genetics Uterus/physiology
Chemicals
RNA, Messenger Sodium Channels DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
George A L
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Knittle T J
Tamkun M M
References (37)
37 references, click to expand
  1. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  2. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs.
    Nucleic Acids Res. 1984 Jan 25;12(2):857-72 PMID: 6694911
  3. Primary structure of the adult human skeletal muscle voltage-dependent sodium channel.
    Ann Neurol. 1992 Feb;31(2):131-7 PMID: 1315496
  4. Pursuing the structure and function of voltage-gated channels.
    Trends Neurosci. 1990 Jun;13(6):201-6 PMID: 1694324
  5. Apamin, a highly potent blocker of the TTX- and Mn2(+)-insensitive fast transient Na+ current in young embryonic heart.
    J Mol Cell Cardiol. 1991 Jan;23(1):25-39 PMID: 2038068
  6. Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle.
    Neuron. 1990 Feb;4(2):233-42 PMID: 2155010
  7. A tetrodotoxin- and Mn2(+)-insensitive Na+ current in Duchenne muscular dystrophy.
    Muscle Nerve. 1990 Oct;13(10):939-48 PMID: 2172811
  8. K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse.
    Science. 1990 May 4;248(4955):599-603 PMID: 2333511
  9. Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.
    Science. 1987 Aug 14;237(4816):744-9 PMID: 2441469
  10. Primary structure of rat brain sodium channel III deduced from the cDNA sequence.
    FEBS Lett. 1988 Feb 8;228(1):187-94 PMID: 2449363
  11. Highly degenerate, inosine-containing primers specifically amplify rare cDNA using the polymerase chain reaction.
    Nucleic Acids Res. 1988 Nov 25;16(22):10932 PMID: 2462716
  12. Molecular diversity of voltage-sensitive Na channels.
    Annu Rev Physiol. 1989;51:401-18 PMID: 2540698
  13. Expression of diverse Na+ channel messenger RNAs in rat myocardium. Evidence for a cardiac-specific Na+ channel.
    J Clin Invest. 1989 Jul;84(1):331-6 PMID: 2544627
  14. Fast Na+ and slow Ca2+ channels in single uterine muscle cells from pregnant rats.
    Am J Physiol. 1989 Aug;257(2 Pt 1):C408-12 PMID: 2548392
  15. Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform.
    Proc Natl Acad Sci U S A. 1989 Oct;86(20):8170-4 PMID: 2554302
  16. Primary structure and functional expression of a mammalian skeletal muscle sodium channel.
    Neuron. 1989 Jul;3(1):33-49 PMID: 2559760
  17. Glial and neuronal forms of the voltage-dependent sodium channel: characteristics and cell-type distribution.
    Neuron. 1989 Apr;2(4):1375-88 PMID: 2560639
  18. Three types of slow inward currents as distinguished by melittin in 3-day-old embryonic heart.
    Can J Physiol Pharmacol. 1988 Aug;66(8):1017-22 PMID: 3179834
  19. Existence of distinct sodium channel messenger RNAs in rat brain.
    Nature. 1986 Mar 13-19;320(6058):188-92 PMID: 3754035
  20. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.
    Nature. 1984 Nov 8-14;312(5990):121-7 PMID: 6209577
  21. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing.
    Gene. 1984 Jun;28(3):351-9 PMID: 6235151
  22. Voltage clamp and internal perfusion of single rat heart muscle cells.
    J Physiol. 1981 Sep;318:455-77 PMID: 7320901
  23. Screening lambdagt recombinant clones by hybridization to single plaques in situ.
    Science. 1977 Apr 8;196(4286):180-2 PMID: 322279
  24. A phosphorylation site in the Na+ channel required for modulation by protein kinase C.
    Science. 1991 Nov 8;254(5033):866-8 PMID: 1658937
  25. Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle.
    FASEB J. 1991 Mar 1;5(3):331-7 PMID: 2001794
  26. Simplified gene nomenclature.
    Nature. 1991 Jul 4;352(6330):26 PMID: 2062374
  27. Cloning and expression of the delayed-rectifier IsK channel from neonatal rat heart and diethylstilbestrol-primed rat uterus.
    Proc Natl Acad Sci U S A. 1990 Apr;87(8):2975-9 PMID: 2183220
  28. High-STX-affinity vs. low-STX-affinity Na+ channel subtypes in nerve, heart, and skeletal muscle.
    Ann N Y Acad Sci. 1986;479:402-30 PMID: 2434005
  29. Structure and function of voltage-sensitive ion channels.
    Science. 1988 Oct 7;242(4875):50-61 PMID: 2459775
  30. Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel.
    Nature. 1989 Jul 20;340(6230):230-3 PMID: 2474130
  31. Structural parts involved in activation and inactivation of the sodium channel.
    Nature. 1989 Jun 22;339(6226):597-603 PMID: 2543931
  32. Molecular analysis of the para locus, a sodium channel gene in Drosophila.
    Cell. 1989 Sep 22;58(6):1143-54 PMID: 2550145
  33. Localization of the receptor site for alpha-scorpion toxins by antibody mapping: implications for sodium channel topology.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):10161-5 PMID: 2557622
  34. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function.
    Science. 1988 Dec 23;242(4886):1654-64 PMID: 3059497
  35. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals.
    Cell. 1987 Jul 31;50(3):509-17 PMID: 3607877
  36. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose.
    Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408-12 PMID: 4504350
  37. Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
    Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):554-8 PMID: 1309946
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.11.4893
Published
1992-06-01
Pages
4893-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49194
Subset
IM
Grants
NIGMS NIH HHS · GM41325 · United States
Databases
GENBANK
M91556
External Links
PubMed source DOI: 10.1073/pnas.89.11.4893 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2