Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain

C. M I Ahmed, D. H. Ware, S. C. Lee, C. D. Patten, A. V. Ferrer-Montiel, A. F. Schinder, John Douglas Mcpherson, C. B. Wagner-McPherson, J. J. Wasmuth, G. A. Evans, M. Montal

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

A cDNA library derived from human cerebral cortex was screened for the presence of sodium channel α subunit-specific clones. Ligation of three overlapping clones generated a full-length cDNA clone, HBA, that provided the complete nucleotide sequence coding for a protein of 2005 amino acids. The predicted structure suggests four homologous repeats and exhibits greatest homology and structural similarity to the rat brain sodium channel II. A second cDNA clone, HBB, that encodes a different subtype of sodium channel was isolated. Hybridization of DNA fragments from the 3' untranslated region of HBA and PCR with primers derived from HBB with human-hamster somatic cell hybrids localized these clones to human chromosome 2. In situ hybridization to human metaphase chromosomes mapped the structural genes for both HBA and HBB sodium channels to chromosome 2q23-24.3. The sodium channel HBA gene product was expressed by transfection in CHO cells. Expressed HBA currents were voltage-dependent, sodium-selective, and tetrodotoxin-sensitive and, thus, exhibit the biophysical and pharmacological properties characteristic of sodium channels.

Original languageEnglish (US)
Pages (from-to)8220-8224
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number17
StatePublished - 1992

    Fingerprint

Keywords

  • chromosome 2
  • excitable membranes
  • human genome
  • ionic channels
  • tetrodotoxin

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Ahmed, C. M. I., Ware, D. H., Lee, S. C., Patten, C. D., Ferrer-Montiel, A. V., Schinder, A. F., Mcpherson, J. D., Wagner-McPherson, C. B., Wasmuth, J. J., Evans, G. A., & Montal, M. (1992). Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain. Proceedings of the National Academy of Sciences of the United States of America, 89(17), 8220-8224.