Neuron
Volume 5, Issue 4, October 1990, Pages 433-443
Journal home page for Neuron

Alteration and restoration of K+ channel function by deletions at the N- and C-termini

https://doi.org/10.1016/0896-6273(90)90082-QGet rights and content

Abstract

Voltage-dependent ion channels are thought to consist of a highly conserved repeated core of six transmembrane segments, flanked by more variable cytoplasmic domains. Significant functional differences exist among related types of K+ channels. These differences have been attributed to the variable domains, most prominently the N- and C-termini. We have therefore investigated the functional importance of both termini for the delayed rectifier K+ channel from rat brain encoded by the drk1 gene. This channel has an unusually long C-terminus. Deletions in either terminus affected both activation and inactivation, in some cases profoundly. Unexpectedly, more extensive deletions in both termini restored gating. We could therefore define a core region only slightly longer than the six transmembrane segments that is sufficient for the formation of channels with the kinetics of a delayed rectifier.

References (53)

  • L.C. Timpe et al.

    Four cDNA clones from the Shaker locus of Drosophila induce kinetically distinct A-type potassium currents in Xenopus oocytes

    Neuron

    (1988)
  • J.S. Trimmer et al.

    Primary structure and functional expression of a mammalian skeletal muscle sodium channel

    Neuron

    (1989)
  • S. Yokoyama et al.

    Potassium channels from NG108-15 neuroblastoma-ghoma hybrid cells: primary structure and functional expression from cDNAs

    FEBS Lett.

    (1989)
  • W.N. Zagotta et al.

    Properties of ShB A-type potassium channels expressed in Shaker mutant Drosophila by germline transformation

    Neuron

    (1989)
  • W. Almers

    Gating currents and charge movements in excitable membranes

    Rev. Physiol. Biochem. Pharmacol.

    (1978)
  • C.M. Armstrong et al.

    Inactivation of the sodium channel. II. Gating current experiments

    J. Gen. Physiol.

    (1977)
  • V.J. Auld et al.

    A neutral amino acid change in segment IIS4 dramatically alters gating properties of the voltage-dependent sodium channel

  • A. Baumann et al.

    Molecular organization of the maternal effect region of the Shaker complex of Drosophila: characterization of an Ia channel transcript with homology to vertebrate Na+ channel

    EMBO J.

    (1987)
  • A. Baumann et al.

    Structure of the voltage-dependent potassium channel is highly conserved from Drosophila to vertebrate central nervous system

    EMBO J.

    (1988)
  • S.L. Berger et al.
  • A. Butler et al.

    A family of putative potassium channel genes in Drosophila

    Science

    (1989)
  • W.A. Catterall

    Structure and function of voltage-sensifive ion channels

    Science

    (1988)
  • L.D. Chabala

    The kinetics of recovery and development of potassium channel inactivation in perfused squid (Loligo pealei) giant axons

    J. Physiol.

    (1984)
  • M.J. Christie et al.

    Expression of a cloned rat brain potassium channel in Xenopus oocytes

    Science

    (1989)
  • J.R. Clay

    Slow inactivation and reactivation of the K channel in squid axons. A tail current analysis

    Biophys. J.

    (1990)
  • J.J. DiStefano et al.

    Multiexponential, multicompartmental, and noncompartmental modeling. II. Data analysis and statistical considerations

    Am. J. Physiol.

    (1984)
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