A mutation in segment I-S6 alters slow inactivation of sodium channels

Biophys J. 1997 Apr;72(4):1633-40. doi: 10.1016/S0006-3495(97)78809-X.


Slow inactivation occurs in voltage-gated Na+ channels when the membrane is depolarized for several seconds, whereas fast inactivation takes place rapidly within a few milliseconds. Unlike fast inactivation, the molecular entity that governs the slow inactivation of Na+ channels has not been as well defined. Some regions of Na+ channels, such as mu1-W402C and mu1-T698M, have been reported to affect slow inactivation. A mutation in segment I-S6 of mu1 Na+ channels, N434A, shifts the voltage dependence of activation and fast inactivation toward the depolarizing direction. The mutant Na+ current at +50 mV is diminished by 60-80% during repetitive stimulation at 5 Hz, resulting in a profound use-dependent phenomenon. This mutant phenotype is due to the enhancement of slow inactivation, which develops faster than that of wild-type channels (tau = 0.46 +/- 0.01 s versus 2.11 +/- 0.10 s at +30 mV, n = 9). An oxidant, chloramine-T, abolishes fast inactivation and yet greatly accelerates slow inactivation in both mutant and wild-type channels (tau = 0.21 +/- 0.02 s and 0.67 +/- 0.05 s, respectively, n = 6). These findings together demonstrate that N434 of mu1 Na+ channels is also critical for slow inactivation. We propose that this slow form of Na+ channel inactivation is analogous to the "C-type" inactivation in Shaker K+ channels.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chloramines / pharmacology
  • Electrophysiology
  • Ion Channel Gating*
  • Kinetics
  • Molecular Sequence Data
  • Muscles
  • Mutagenesis, Site-Directed
  • Patch-Clamp Techniques
  • Potassium Channels / metabolism
  • Rats
  • Shaker Superfamily of Potassium Channels
  • Sodium Channels / genetics*
  • Sodium Channels / metabolism*
  • Tosyl Compounds / pharmacology


  • Chloramines
  • Potassium Channels
  • Shaker Superfamily of Potassium Channels
  • Sodium Channels
  • Tosyl Compounds
  • chloramine-T