Regulation of Kv4.2 channels by glutamate in cultured hippocampal neurons

Lei, Zhigang; Deng, Ping; Xu, Zao C.

doi:10.1111/j.1471-4159.2008.05356.x

Cited by 29 publications

(41 citation statements)

References 59 publications

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“…Sustained excitation produced by exogenous glutamate enhances A-type currents decreasing neuronal excitability in cortical neurons (Shen et al, 2008, but see Lei et al, 2008 in hippocampal neurons), and shifts the voltage activation curve of sustained currents toward more hyperpolarized potentials in hippocampal neurons (Misonou et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…NMDA receptors play a pivotal role in transmission along nociceptive pathways, and their activation has been shown to modulate potassium currents in other systems (Lei et al, 2008;Mulholland et al, 2008;Shen et al, 2008). Here we superfused the cord with NMDA (20 min) at a concentration sufficient to produce sustained firing (10 M) and then recorded dorsal horn neurons in a time window between 1 and 4 h after NMDA perfusion.…”

Section: Modulation Of Outward Potassium Currents By Nmda Receptor Acmentioning

confidence: 99%

“…However, recent evidence indicates that Kv4.2 channels underlay A-type currents in mice dorsal horn neurons and that the genetic elimination of this channel prevents a normal hyperalgesic response to inflammatory stimuli (Hu et al, 2006). Transient and sustained potassium currents (A-type and delayed rectifier type currents) influence membrane excitability and are modulated by activity-dependent mechanisms (Desai et al, 1999;Yoshimura and de Groat, 1999;Stewart et al, 2003;Dang et al, 2004;Misonou et al, 2004;Takeda et al, 2006;van Welie et al, 2006;Xu et al, 2006;Wang et al, 2007;Lei et al, 2008;Shen et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Changes in Membrane Excitability and Potassium Currents in Sensitized Dorsal Horn Neurons of Mice Pups

Rivera-Arconada¹,

López-García²

2010

J. Neurosci.

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Rationally, an increased intrinsic excitability of dorsal horn neurons could be a factor contributing to alter the gain of the nociceptive system during central sensitization, however direct evidence is scarce. Here we have examined this hypothesis using current and voltageclamp recordings from dorsal horn neurons in the spinal cord in vitro preparation obtained from mice pups of either sex. Cords were extracted from carrageenan-pretreated and control animals to allow for comparison. Dorsal horn neurons from treated animals showed significantly larger and faster synaptic responses. Synaptic changes started developing shortly after inflammation (1 h) and developed further after a longer-term inflammation (20 h). However, these neurons showed biphasic changes in membrane excitability with an increase shortly after inflammation and a decrease in the longer term. Concomitant changes were observed in transient (I A ) and sustained potassium currents (I DR ). Prolonged superfusion of naive spinal cords with NMDA led to a decreased neuronal excitability and to increased potassium currents.Results suggest that excitability plays a role more complex than expected during the process of central sensitization of dorsal horn neurons and that modulation of potassium currents may contribute to shape the changing states of excitability. The decreased excitability observed after long-term inflammation is interpreted as a homeostatic correction to an abnormal state of synaptic activity.

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Section: Discussionmentioning

confidence: 99%

Section: Modulation Of Outward Potassium Currents By Nmda Receptor Acmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Changes in Membrane Excitability and Potassium Currents in Sensitized Dorsal Horn Neurons of Mice Pups

Rivera-Arconada¹,

López-García²

2010

J. Neurosci.

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“…As glutamate receptor stimulation induces the internalization of Kv4 channels in hippocampal neurons (Kim et al, 2007;Lei et al, 2008), we next tested whether glutamate could affect IK A amplitude in cerebellar PCs. Glutamate and AMPA, but not NMDA (in the presence of 1.19 mM MgSO 4 in the extracellular solution), reduced IK A by ϳ30% in WT PCs and ϳ45% in SCA1 PCs (Fig.…”

Section: Motor Impairment Precedes Morphological Changes and Loss Of mentioning

confidence: 99%

Aminopyridines Correct Early Dysfunction and Delay Neurodegeneration in a Mouse Model of Spinocerebellar Ataxia Type 1

Hourez¹,

Servais²,

Orduz³

et al. 2011

J. Neurosci.

140

159

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The contribution of neuronal dysfunction to neurodegeneration is studied in a mouse model of spinocerebellar ataxia type 1 (SCA1) displaying impaired motor performance ahead of loss or atrophy of cerebellar Purkinje cells. Presymptomatic SCA1 mice show a reduction in the firing rate of Purkinje cells (both in vivo and in slices) associated with a reduction in the efficiency of the main glutamatergic synapse onto Purkinje cells and with increased A-type potassium current. The A-type potassium channel Kv4.3 appears to be internalized in response to glutamatergic stimulation in Purkinje cells and accumulates in presymptomatic SCA1 mice. SCA1 mice are treated with aminopyridines, acting as potassium channel blockers to test whether the treatment could improve neuronal dysfunction, motor behavior, and neurodegeneration. In acutely treated young SCA1 mice, aminopyridines normalize the firing rate of Purkinje cells and the motor behavior of the animals. In chronically treated old SCA1 mice, 3,4-diaminopyridine improves the firing rate of Purkinje cells, the motor behavior of the animals, and partially protects against cell atrophy. Chronic treatment with 3,4-diaminopyridine is associated with increased cerebellar levels of BDNF, suggesting that partial protection against atrophy of Purkinje cells is possibly provided by an increased production of growth factors secondary to the reincrease in electrical activity. Our data suggest that aminopyridines might have symptomatic and/or neuroprotective beneficial effects in SCA1, that reduction in the firing rate of Purkinje cells can cause cerebellar ataxia, and that treatment of early neuronal dysfunction is relevant in neurodegenerative disorders such as SCA1.

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“…Somatodendritic IA current performs a pivotal function in synaptic integration and synaptic plasticity, by modulating membrane excitability or by inhibiting the back-propagation of dendritic APs (3-7). Kv4.2, a pore-forming α-subunit of voltage-gated A-type potassium channels, is expressed abundantly within the soma and dendrites of hippocampal neurons (8)(9)(10)(11), and is responsible for most of the somatodendritic IA current (7,(11)(12)(13) -dependent down-regulation of Kv4.2 channels in the membrane surfaces of hippocampal neurons (14,15).…”

Section: Introductionmentioning

confidence: 99%

Dendritic localization and a cis-acting dendritic targeting element of Kv4.2 mRNA

Nam²,

Oh³

et al. 2010

BMB Reports

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Kv4.2, a pore-forming α-subunit of voltage-gated A-type potassium channels, is expressed abundantly in the soma and dendrites of hippocampal neurons, and is responsible for somatodendritic IA current. Recent studies have suggested that changes in the surface levels of Kv4.2 potassium channels might be relevant to synaptic plasticity. Although the function and expression of Kv4.2 protein have been extensively studied, the dendritic localization of Kv4.2 mRNA is not well described. In this study, Kv4.2 mRNAs were shown to be localized in the dendrites near postsynaptic regions. The dendritic transport of Kv4.2 mRNAs were mediated by microtubule-based movement. The 500 nucleotides of specific regions within the 3'-untranslated region of Kv4.2 mRNA were found to be necessary and sufficient for its dendritic localization. Collectively, these results suggest that the dendritic localization of Kv4.2 mRNAs might regulate the dendritic surface level of Kv4.2 channels and synaptic plasticity. [BMB reports 2010; 43(10): 677-682]

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Regulation of Kv4.2 channels by glutamate in cultured hippocampal neurons

Cited by 29 publications

References 59 publications

Changes in Membrane Excitability and Potassium Currents in Sensitized Dorsal Horn Neurons of Mice Pups

Changes in Membrane Excitability and Potassium Currents in Sensitized Dorsal Horn Neurons of Mice Pups

Aminopyridines Correct Early Dysfunction and Delay Neurodegeneration in a Mouse Model of Spinocerebellar Ataxia Type 1

Dendritic localization and a cis-acting dendritic targeting element of Kv4.2 mRNA

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