Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel

Mary E. Gellens, Alfred L. George, Liqiong Chen, Mohamed Chahine, Richard Horn, Robert Barchi, Roland G. Kallen

Research output: Contribution to journalArticle

512 Citations (Scopus)

Abstract

The principal voltage-sensitive sodium channel from human heart has been cloned, sequenced, and functionally expressed. The cDNA, designated hH1, encodes a 2016-amino acid protein that is homologous to other members of the sodium channel multigene family and bears >90% identity to the tetrodotoxin-insensitive sodium channel characteristic of rat heart and of immature and denervated rat skeletal muscle. Northern blot analysis demonstrates an ≈9.0-kilobase transcript expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. When expressed in Xenopus oocytes, hHl exhibits rapid activation and inactivation kinetics similar to native cardiac sodium channels. The single channel conductance of hH1 to sodium ions is about twice that of the homologous rat channel and hH1 is more resistant to block by tetrodotoxin (IC50 = 5.7 μM). hH1 is also resistant to μ-conotoxin but sensitive to block by therapeutic concentrations of lidocaine in a use-dependent manner.

Original languageEnglish (US)
Pages (from-to)554-558
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number2
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

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Sodium Channels
Tetrodotoxin
Skeletal Muscle
Conotoxins
Myometrium
Multigene Family
Xenopus
Lidocaine
Northern Blotting
Inhibitory Concentration 50
Oocytes
Myocardium
Spleen
Complementary DNA
Sodium
Ions
Amino Acids
Liver
Brain
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Gellens, Mary E. ; George, Alfred L. ; Chen, Liqiong ; Chahine, Mohamed ; Horn, Richard ; Barchi, Robert ; Kallen, Roland G. / Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 2. pp. 554-558.
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Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. / Gellens, Mary E.; George, Alfred L.; Chen, Liqiong; Chahine, Mohamed; Horn, Richard; Barchi, Robert; Kallen, Roland G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 2, 01.01.1992, p. 554-558.

Research output: Contribution to journalArticle

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AU - George, Alfred L.

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AU - Horn, Richard

AU - Barchi, Robert

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