Elsevier

NeuroToxicology

Volume 26, Issue 5, October 2005, Pages 743-752
NeuroToxicology

Review
Kv2.1: A Voltage-Gated K+ Channel Critical to Dynamic Control of Neuronal Excitability

https://doi.org/10.1016/j.neuro.2005.02.003Get rights and content

Abstract

Neurons use a variety of mechanisms to dynamically control their own signaling capabilities. Regulation of voltage-dependent K+ channel localization and function has long been recognized as a major mechanism to achieve dynamic regulation of intrinsic neuronal excitability in a number of mammalian and non-mammalian neurons. Our recent evidence, together with compelling data from other laboratories, suggests that in mammalian neurons the Kv2.1 channel may play an especially prominent role in determining intrinsic neuronal excitability. Kv2.1 is widely expressed in brain and composes the majority of delayed rectifier K+ current in pyramidal neurons in cortex and hippocampus, and is also widely expressed in interneurons. Dynamic modulation of Kv2.1 localization and function by a mechanism involving activity-dependent Kv2.1 dephosphorylation dramatically impacts intrinsic excitability of neurons. Here we review previous studies of Kv2.1 localization and function in neurons, and summarize recent work regarding dynamic regulation of these characteristics. We also discuss possible roles of the Kv2.1 channel in neuronal and network excitability.

Section snippets

INTRODUCTION

Dynamic regulation of the intrinsic electrical excitability of neurons confers plasticity to neuronal function (Daoudal and Debanne, 2003). Neurons use a wide variety of mechanisms to precisely control electrical excitability. Voltage-dependent K+ (Kv) channels are especially diverse components of the channel repertoire that determine a neuron's intrinsic electrical excitability (Pongs, 1999). Neurons express a wide variety of Kv channels that can contribute to diverse aspects of neuronal

BIOSYNTHESIS, POST-TRANSLATIONAL MODIFICATIONS, AND INTRACELLULAR TRAFFICKING OF Kv2.1

Individual Kv channel Kv2.1 α subunit polypeptides have six transmembrane segments (termed S1–S6) and assemble post-translationally to form tetrameric complexes (Fig. 1). The ≈300 amino acid core domains containing the transmembrane S1–S6 segments present in each of the four α subunits co-assemble to form the major portions of both the voltage-sensing apparatus and ion-selective pore. Amino- and carboxyl-termini are cytoplasmic, such that all extracellular domains are found within the core

DYNAMIC MODULATION OF Kv2.1 IN NEURONAL ACTIVITY AND ITS ROLE IN NEURONAL SIGNALING

Persistent changes in intrinsic neuronal excitability in the face of sustained changes in synaptic input have been reported in different type of neurons. This phenomenon, a form of homeostatic plasticity (also as cellular or intrinsic plasticity), alters overall input–output function of a neuron and thus stabilize neuronal circuits by setting the optimal output level of each elements of the circuitry (Cantrell and Catterall, 2001, Daoudal and Debanne, 2003, Desai et al., 1999, Marder and Prinz,

POTENTIAL ROLES OF Kv2.1 IN NEURONS

Kv2.1, the major IK channel in cultured hippocampal neurons, is expressed at a very high level in virtually all brain neurons. This particular abundance presumably reflects a fundamental and general role for Kv2.1 in neurons. Kv2.1 has a single channel conductance of ∼10 pS when expressed in Xenopus oocytes (Chapman et al., 2001, Pascual et al., 1997, Taglialatela and Stefani, 1993). The activation and inactivation time constants are ∼10 ms (at 0 mV) and ∼3–5 s (at 10 mV in Xenopus oocytes),

Acknowledgement

Supported by NIH grant NS42225 (to JST).

References (62)

  • A.B. Nelson et al.

    Long-lasting increases in intrinsic excitability triggered by inhibition

    Neuron

    (2003)
  • O. Pongs

    Voltage-gated potassium channels: from hyperexcitability to excitement

    FEBS Lett

    (1999)
  • G. Shi et al.

    Properties of Kv2.1 K+ channels expressed in transfected mammalian cells

    J Biol Chem

    (1994)
  • R. Shibata et al.

    A fundamental role for KChlPs in determining the molecular properties and trafficking of Kv4.2 potassium channels

    J Biol Chem

    (2003)
  • W.J. Song

    Genes responsible for native depolarization-activated K+ currents in neurons

    Neurosci Res

    (2002)
  • N.C. Spitzer et al.

    Outside and in: development of neuronal excitability

    Curr Opin Neurobiol

    (2002)
  • H. Taschenberger et al.

    Interaction of calcium-permeable non-N-methyl-d-aspartate receptor channels with voltage-activated potassium and calcium currents in rat retinal ganglion cells in vitro

    Neuroscience

    (1998)
  • Z. Tiran et al.

    Phosphorylation-dependent regulation of Kv2.1 channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase epsilon

    J Biol Chem

    (2003)
  • A.M. VanDongen et al.

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

    Neuron

    (1990)
  • A. Wickenden

    K(+) channels as therapeutic drug targets

    Pharmacol Ther

    (2002)
  • E. Aizenman et al.

    Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular zinc release

    J Neurochem

    (2000)
  • J.M. Bekkers

    Distribution and activation of voltage-gated potassium channels in cell-attached and outside-out patches from large layer 5 cortical pyramidal neurons of the rat

    J Physiol

    (2000)
  • A.R. Cantrell et al.

    Neuromodulation of Na+ channels: an unexpected form of cellular plasticity

    Nat Rev Neurosci

    (2001)
  • M.L. Chapman et al.

    GYGD pore motifs in neighbouring potassium channel subunits interact to determine ion selectivity

    J Physiol

    (2001)
  • H.J. Chung et al.

    Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins

    J Neurosci

    (2000)
  • C.M. Colbert et al.

    Arachidonic acid reciprocally alters the availability of transient and sustained dendritic K(+) channels in hippocampal CA1 pyramidal neurons

    J Neurosci

    (1999)
  • G. Daoudal et al.

    Long-term plasticity of intrinsic excitability: learning rules and mechanisms

    Learn Mem

    (2003)
  • G. Daoudal et al.

    Bidirectional plasticity of excitatory postsynaptic potential (EPSP)-spike coupling in CA1 hippocampal pyramidal neurons

    Proc Natl Acad Sci USA

    (2002)
  • N.S. Desai et al.

    Plasticity in the intrinsic excitability of cortical pyramidal neurons

    Nat Neurosci

    (1999)
  • J. Du et al.

    Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K+ channel subunit Kv2.1

    J Physiol

    (2000)
  • G. Frech et al.

    A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning

    Nature

    (1989)
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