Slow inactivation of the NaV1.4 sodium channel in mammalian cells is impeded by co-expression of the β1 subunit

Ion Channels, Receptors and Transporters

DOI: 10.1007/s00424-008-0600-8

Cite this article as:
Webb, J., Wu, F. & Cannon, S.C. Pflugers Arch - Eur J Physiol (2009) 457: 1253. doi:10.1007/s00424-008-0600-8


In response to sustained depolarization or prolonged bursts of activity in spiking cells, sodium channels enter long-lived non-conducting states from which recovery at hyperpolarized potentials occurs over hundreds of milliseconds to seconds. The molecular basis for this slow inactivation remains unknown, although many functional domains of the channel have been implicated. Expression studies in Xenopus oocytes and mammalian cell lines have suggested a role for the accessory β1 subunit in slow inactivation, but the effects have been variable. We examined the effects of the β1 subunit on slow inactivation of skeletal muscle (NaV1.4) sodium channels expressed in HEK cells. Co-expression of the β1 subunit impeded slow inactivation elicited by a 30-s depolarization, such that the voltage dependence was right shifted (depolarized) and recovery was hastened. Mutational studies showed this effect was dependent upon the extracellular Ig-like domain, but was independent of the intracellular C-terminal tail. Furthermore, the β1 effect on slow inactivation was shown to be independent of the negative coupling between fast and slow inactivation.


Gating SCN4A SCN1B Mammalian expression system Skeletal muscle Voltage-gated sodium channel 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Neuroscience ProgramUT Southwestern Medical CenterDallasUSA
  2. 2.Department of NeurologyUniversity of Texas Southwestern Medical CenterDallasUSA

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