Review
Dendritic ion channel trafficking and plasticity

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Dendritic ion channels are essential for the regulation of intrinsic excitability as well as modulating the shape and integration of synaptic signals. Changes in dendritic channel function have been associated with many forms of synaptic plasticity. Recent evidence suggests that dendritic ion channel modulation and trafficking could contribute to plasticity-induced alterations in neuronal function. In this review we discuss our current knowledge of dendritic ion channel modulation and trafficking and their relationship to cellular and synaptic plasticity. We also consider the implications for neuronal function. We argue that to gain an insight into neuronal information processing it is essential to understand the regulation of dendritic ion channel expression and properties.

Section snippets

Dendrites and plasticity

Dendrites are extensive and elaborate processes emerging from the cell body of neurons. They occupy a large surface area and receive most synaptic inputs [1]. Their predominant function is in processing and transmitting synaptic signals to the cell body and axon initial segment, where, if threshold is reached, action potentials are initiated. This is an active process because it is known that dendrites possess an abundance of ion channels that are involved in receiving, transforming and

Role of dendritic ion channels in regulating intrinsic excitability, synaptic integration and plasticity

Dendrites contain a plethora of ion channels including K+ channels. In many central neurons the densities of most voltage-gated potassium (Kv) channels appear to be uniform or lower in distal dendrites compared with those at the soma [1]. One exception appears to be the Kv4 subunit. Immunohistochemical analysis first showed a predominantly dendritic localization of Kv4 channels [16] (Table 1). The Kv4 subunits form a fast activating and inactivating current in heterologous systems, reminiscent

Plasticity-induced post-translational modifications and membrane trafficking of dendritic ion channels

Cellular neuroplasticity has been hypothesized to underlie experience-dependent behaviors such as learning and memory and drug addiction (Figure 1). Uncovering the cellular and molecular mechanisms of the acquisition, storage and recollection of memories is a major topic of basic and translational neuroscience research because alterations in these mechanisms could contribute to multiple disease pathologies, including autism, epilepsy, Alzheimer's and Parkinson's disease. For the most part,

Concluding remarks

In summary, we have discussed how the activity and expression of dendritic ion channels can be dynamically regulated by alterations in intrinsic neuronal firing and changes in synaptic activity. Whereas enormous strides have been made in understanding how several subtypes of voltage-gated ion channels are selectively targeted to dendrites and how plasticity affects the dendritic trafficking of these channels, much less is known about others. For example, dendritic Na+ and Ca2+ channel function

Acknowledgements

This work was supported by an New Investigator Award from the Medical Research Council (G0700369, M.M.S.), a Wellcome Trust project grant (WT087363MA, M.M.S.) and the Intramural Research Program of the National Institutes of Health and the National Institute of Child Health and Human Development (D.H.).

References (110)

  • S. Peleg

    i controls the gating of the G protein-activated K+ channel

    GIRK. Neuron

    (2002)
  • C.S. Huang

    Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition

    Cell

    (2005)
  • C. Luscher

    G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons

    Neuron

    (1997)
  • M.M. Shah

    Seizure-induced plasticity of h channels in entorhinal cortical layer III pyramidal neurons

    Neuron

    (2004)
  • D. Tsay

    HCN1 channels constrain synaptically evoked Ca2+ spikes in distal dendrites of CA1 pyramidal neurons

    Neuron

    (2007)
  • M.F. Nolan

    A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons

    Cell

    (2004)
  • M. Wang

    Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP–HCN channel signaling in prefrontal cortex

    Cell

    (2007)
  • B.L. Bloodgood et al.

    Ca2+ signaling in dendritic spines

    Curr. Opin. Neurobiol.

    (2007)
  • Y. Humeau et al.

    Dendritic calcium spikes induce bi-directional synaptic plasticity in the lateral amygdala

    Neuropharmacology

    (2007)
  • H. Takahashi et al.

    Pathway interactions and synaptic plasticity in the dendritic tuft regions of CA1 pyramidal neurons

    Neuron

    (2009)
  • J. Kim

    Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons

    Neuron

    (2007)
  • P.J. Chu

    A role for Kif17 in transport of Kv4.2

    J. Biol. Chem.

    (2006)
  • X. Ren

    Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels

    Mol. Cell Neurosci.

    (2005)
  • L. Lin

    KChIP4a regulates Kv4.2 channel trafficking through PKA phosphorylation

    Mol. Cell Neurosci.

    (2010)
  • M.E. Larkum

    Synaptic integration in tuft dendrites of layer 5 pyramidal neurons: a new unifying principle

    Science

    (2009)
  • T. Nevian

    Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study

    Nat. Neurosci.

    (2007)
  • C.D. Acker et al.

    Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites

    J. Neurophysiol.

    (2009)
  • L.F. Abbott et al.

    Synaptic plasticity: taming the beast

    Nat. Neurosci.

    (2000)
  • P.J. Sjostrom

    Dendritic excitability and synaptic plasticity

    Physiol. Rev.

    (2008)
  • A. Frick et al.

    Plasticity of dendritic excitability

    J. Neurobiol.

    (2005)
  • H.C. Lai et al.

    The distribution and targeting of neuronal voltage-gated ion channels

    Nat. Rev.

    (2006)
  • C.R. Bramham et al.

    Dendritic mRNA: transport, translation and function

    Nat. Rev.

    (2007)
  • O. Steward et al.

    Protein synthesis at synaptic sites on dendrites

    Annu. Rev. Neurosci.

    (2001)
  • G.A. Kerchner et al.

    Silent synapses and the emergence of a postsynaptic mechanism for LTP

    Nat. Rev.

    (2008)
  • P. Serodio

    Identification of molecular components of A-type channels activating at subthreshold potentials

    J. Neurophysiol.

    (1994)
  • J.M. Christie et al.

    Regulation of backpropagating action potentials in mitral cell lateral dendrites by A-type potassium currents

    J. Neurophysiol.

    (2003)
  • D.A. Hoffman

    K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons

    Nature

    (1997)
  • N.E. Schoppa et al.

    Regulation of synaptic timing in the olfactory bulb by an A-type potassium current

    Nat. Neurosci.

    (1999)
  • G.J. Stuart et al.

    Dendritic coincidence detection of EPSPs and action potentials

    Nat. Neurosci.

    (2001)
  • A. Frick

    Normalization of Ca2+ signals by small oblique dendrites of CA1 pyramidal neurons

    J. Neurosci.

    (2003)
  • A. Losonczy

    Compartmentalized dendritic plasticity and input feature storage in neurons

    Nature

    (2008)
  • B.M. Kampa et al.

    Calcium spikes in basal dendrites of layer 5 pyramidal neurons during action potential bursts

    J. Neurosci.

    (2006)
  • J. Kim

    Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones

    J. Physiol.

    (2005)
  • X. Chen

    Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons

    J. Neurosci.

    (2006)
  • H. Vacher

    Localization and targeting of voltage-dependent ion channels in mammalian central neurons

    Physiol. Rev.

    (2008)
  • P.D. Sarmiere

    The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ

    BMC Neurosci.

    (2008)
  • J. Du

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

    J. Physiol.

    (2000)
  • T.J. Ngo-Anh

    SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines

    Nat. Neurosci.

    (2005)
  • E.S. Faber

    SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala

    Nat. Neurosci.

    (2005)
  • M.D. Womack et al.

    Dendritic control of spontaneous bursting in cerebellar Purkinje cells

    J. Neurosci.

    (2004)
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