Interaction between the sodium channel inactivation linker and domain III S4-S5

Biophys J. 1997 Oct;73(4):1885-95. doi: 10.1016/S0006-3495(97)78219-5.


The III-IV linker (L(III-IV)) of the rat brain sodium channel is critical for fast inactivation, possibly forming a fast inactivation particle. Inactivation can be disrupted by mutation of a conserved alanine at position 1329 in the S4-S5 loop of domain III. Combination of a charged mutation at 1329 with a compensatory (opposite) charge mutation at position 1489 in L(III-IV) partially restores inactivation of the channel. The compensatory charge mutant channel has a single-channel mean open time that is similar to that of the wild-type channel and is approximately 50 times shorter than that of the L(III-IV) mutant channel. The results of thermodynamic cycle analysis indicate that the mutations in domain III S4-S5 and L(III-IV) have a coupling energy of 2.8 kcal/mol, indicating that the two mutations act interdependently. These data suggest that L(III-IV) interacts directly with A1329, which may form part of the docking site if L(III-IV) is a fast inactivation particle.

Publication types

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

MeSH terms

  • Action Potentials
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Biophysical Phenomena
  • Biophysics
  • Brain / metabolism
  • DNA Primers / genetics
  • Female
  • In Vitro Techniques
  • Ion Channel Gating
  • Kinetics
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes / metabolism
  • Rats
  • Sodium Channel Blockers*
  • Sodium Channels / chemistry*
  • Sodium Channels / genetics
  • Thermodynamics
  • Xenopus laevis


  • DNA Primers
  • Sodium Channel Blockers
  • Sodium Channels