Journal of Comparative Physiology A

, Volume 199, Issue 10, pp 829–842

A naturally occurring amino acid substitution in the voltage-dependent sodium channel selectivity filter affects channel gating

Authors

    • Section of Neurobiology, Institute for NeuroscienceUniversity of Texas at Austin
  • Na Ye
    • Section of Neurobiology, Institute for NeuroscienceUniversity of Texas at Austin
  • Biswa Sengupta
    • The Wellcome Trust Centre for NeuroimagingUniversity College London
    • Centre for NeuroscienceIndian Institute of Science
  • Harold H. Zakon
    • Section of Neurobiology, Institute for NeuroscienceUniversity of Texas at Austin
Original Paper

DOI: 10.1007/s00359-013-0845-3

Cite this article as:
Wu, M., Ye, N., Sengupta, B. et al. J Comp Physiol A (2013) 199: 829. doi:10.1007/s00359-013-0845-3

Abstract

The pore of sodium channels contains a selectivity filter made of 4 amino acids, D/E/K/A. In voltage sensitive sodium channel (Nav) channels from jellyfish to human the fourth amino acid is Ala. This Ala, when mutated to Asp, promotes slow inactivation. In some Nav channels of pufferfishes, the Ala is replaced with Gly. We studied the biophysical properties of an Ala-to-Gly substitution (A1529G) in rat Nav1.4 channel expressed in Xenopus oocytes alone or with a β1 subunit. The Ala-to-Gly substitution does not affect monovalent cation selectivity and positively shifts the voltage-dependent inactivation curve, although co-expression with a β1 subunit eliminates the difference between A1529G and WT. There is almost no difference in channel fast inactivation, but the β1 subunit accelerates WT current inactivation significantly more than it does the A1529G channels. The Ala-to-Gly substitution mainly influences the rate of recovery from slow inactivation. Again, the β1 subunit is less effective on speeding recovery of A1529G than the WT. We searched Nav channels in numerous databases and noted at least four other independent Ala-to-Gly substitutions in Nav channels in teleost fishes. Thus, the Ala-to-Gly substitution occurs more frequently than previously realized, possibly under selection for alterations of channel gating.

Keywords

Voltage-gated sodium channelA1529GSlow inactivationSelectivity filter

Copyright information

© Springer-Verlag Berlin Heidelberg 2013