A molecular basis for gating mode transitions in human skeletal muscle Na+ channels

FEBS Lett. 1993 Jul 12;326(1-3):21-4. doi: 10.1016/0014-5793(93)81752-l.

Abstract

Recombinant sodium channel alpha subunits expressed in Xenopus oocytes display an anomalously slow rate of inactivation that arises from channels that predominantly exist in a slow gating mode [1,2]. Co-expression of Na+ channel beta 1 subunit with the human skeletal muscle Na+ channel alpha subunit increases the Na+ current and induces normal gating behavior in Xenopus laevis oocytes. The effects of the beta 1 subunit can be explained by an allosterically induced conformational switch of the alpha subunit protein that occurs upon binding the beta 1 subunit. This binding alters the free energy barriers separating distinct conformational states of the channel. The results illustrate a fundamental modulation of ion channel gating at the molecular level, and specifically demonstrate the importance of the beta 1 subunit for gating mode changes of Na+ channels.

Publication types

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

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry, Physical
  • Electric Conductivity
  • Female
  • Humans
  • Ion Channel Gating*
  • Muscles / physiology*
  • Oocytes / physiology
  • Protein Conformation
  • Rats
  • Recombinant Proteins
  • Sodium / metabolism
  • Sodium Channels / chemistry
  • Sodium Channels / genetics
  • Sodium Channels / physiology*
  • Xenopus laevis

Substances

  • Recombinant Proteins
  • Sodium Channels
  • Sodium