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Pflügers Archiv

, Volume 428, Issue 3–4, pp 382–390 | Cite as

Properties of voltage-gated K+ currents expressed inXenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1

  • William F. Hopkins
  • Margaret L. Allen
  • Khaled M. Houamed
  • Bruce L. Tempel
Molecular and Cellular Physiology

Abstract

Two similar mouseShaker-like K+ channel genes, mKv1.1 and mKv1.2, have been shown to form heteromultimers in vivo. The predicted amino acid sequence of each channel is nearly identical in mice, rats and humans, suggesting that each has been highly conserved evolutionarily. Here we report the biophysical and pharmacological properties of each channel when expressed alone or when coexpressed inXenopus oocytes. The voltage sensitivities of activation were similar for both, but the voltages at which the K+ conductances were half-maximal (V1/2) were −37 mV and −27 mV for mKv1.1 and mKv1.2 respectively. Both displayed voltage-dependent, but incomplete, inactivation following a prepulse with mKv1.2 showing the greater degree of inactivation. For mKv1.1, the onset and recovery from inactivation could be described by single, slow time constants (2–4 s), whereas for mKv1.2 the onset and recovery from inactivation displayed a second, faster time constant (< 400 ms). Using a mutant mKv1.1 that is 100-fold less sensitive to dendrotoxin-I than mKv1.1, we demonstrate that this mutant mKv1.1 and wild-type mKv1.2 subunits can form heteromultimeric channels. With some exceptions, of unknown significance, the biophysical properties of the heteromultimeric channels formed by wild-type mKv1.1 and mKv1.2 subunits were intermediate between those of mKv1.1 and mKv1.2 homomultimers, but quantitatively more similar to the more abundant subunit.

Key words

K+ channels Inactivation Tetraethyl-ammonium Dendrotoxin Site-directed mutagenesis Heteromultimer 

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • William F. Hopkins
    • 1
    • 2
  • Margaret L. Allen
    • 1
    • 2
  • Khaled M. Houamed
    • 3
  • Bruce L. Tempel
    • 1
    • 2
  1. 1.Geriatric Research Education and Clinical Center (182-B)Veterans Affairs Medical CenterSeattleUSA
  2. 2.Departments of Medicine and Pharmacology (SJ-30)University of Washington School of MedicineSeattleUSA
  3. 3.Department of Molecular Pharmacology, Biosciences DivisionNovo Nordisk, Novo AlleBagsvaerdDenmark

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