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

Alfred L. George, Timothy J. Knittle, Michael M. Tamkun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

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 a subunit that exhibits only moderate primary structure identity with other sodium channels and is prominently expressed in both heart and uterus. The ≈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.

Original languageEnglish (US)
Pages (from-to)4893-4897
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number11
DOIs
StatePublished - 1992

Keywords

  • Cardiovascular system
  • Complementary DNA
  • Heart muscle
  • Skeletal muscle

ASJC Scopus subject areas

  • General

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