Modulation of cardiac Na+ channel expression in Xenopus oocytes by beta 1 subunits

J Biol Chem. 1995 Oct 27;270(43):25696-701. doi: 10.1074/jbc.270.43.25696.

Abstract

Voltage-gated Na+ channels consist of a large alpha subunit of 260 kDa associated with beta 1 and/or beta 2 subunits of 36 and 33 kDa, respectively. alpha subunits of rat cardiac Na+ channels (rH1) are functional when expressed alone in Xenopus oocytes or mammalian cells. beta 1 subunits are present in the heart, and localization of beta 1 subunit mRNA by in situ hybridization shows expression in the perinuclear cytoplasm of cardiac myocytes. Coexpression of beta 1 subunits with rH1 alpha subunits in Xenopus oocytes increases Na+ currents up to 6-fold in a concentration-dependent manner. However, no effects of beta 1 subunit coexpression on the kinetics or voltage dependence of the rH1 Na+ current were detected. Increased expression of Na+ currents is not observed when an equivalent mRNA encoding a nonfunctional mutant beta 1 subunit is coexpressed. Our results show that beta 1 subunits are expressed in cardiac muscle cells and that they interact with alpha subunits to increase the expression of cardiac Na+ channels in Xenopus oocytes, suggesting that beta 1 subunits are important determinants of the level of excitability of cardiac myocytes in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Brain / metabolism
  • Cell Membrane / metabolism
  • Cytoplasm / ultrastructure
  • Electric Conductivity
  • Female
  • In Situ Hybridization
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Oocytes
  • Patch-Clamp Techniques
  • Protein Conformation
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Sodium / metabolism
  • Sodium Channels / biosynthesis*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • Xenopus

Substances

  • RNA, Messenger
  • Recombinant Proteins
  • Sodium Channels
  • Sodium