INT169560

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Context Info
Confidence 0.54
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 20
Total Number 25
Disease Relevance 6.83
Pain Relevance 2.64

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

Anatomy Link Frequency
microglia 4
neurons 3
SK-N-FI 2
SK-N-SH 2
bar 1
SK (Mus musculus)
Pain Link Frequency Relevance Heat
amygdala 65 99.98 Very High Very High Very High
Inflammation 70 98.60 Very High Very High Very High
Potency 65 98.20 Very High Very High Very High
long-term potentiation 104 98.00 Very High Very High Very High
Pyramidal cell 260 97.42 Very High Very High Very High
cytokine 7 97.12 Very High Very High Very High
Dopamine 91 94.88 High High
Limbic system 26 92.16 High High
Substantia nigra 97 91.44 High High
Neuronal excitability 45 91.28 High High
Disease Link Frequency Relevance Heat
Cancer 348 99.48 Very High Very High Very High
INFLAMMATION 77 98.60 Very High Very High Very High
Targeted Disruption 39 98.24 Very High Very High Very High
Drug Induced Neurotoxicity 43 97.12 Very High Very High Very High
Apoptosis 56 96.68 Very High Very High Very High
Neuroblastoma 315 95.64 Very High Very High Very High
Ataxia 104 92.44 High High
Urological Neuroanatomy 13 88.08 High High
Hemorrhage 6 85.12 High High
Epilepsy 84 83.20 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
These cascade of events include the activation of sphingosine kinase (SK), and subsequent production of the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P).
Gene_expression (production) of SK
1) Confidence 0.54 Published 2010 Journal Carcinogenesis Section Abstract Doc Link 20688834 Disease Relevance 0.74 Pain Relevance 0.23
Cultured microglial cells from rat and mouse brain have been shown to express both SK (SK2, SK3) and IK channels [173, 174].
Gene_expression (express) of SK in microglial cells
2) Confidence 0.19 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.10 Pain Relevance 0.07
As for the effect of PKA phosphorylation on SK channels natively expressed in neurons, a recent study has shown that during LTP induction SK2 channels are internalized from the postsynaptic density into CA1 dendritic spines in a PKA-dependent manner [84].
Gene_expression (expressed) of SK in neurons associated with long-term potentiation
3) Confidence 0.19 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.23
The impact of SK channels on the function of DCN neurons has been further corroborated by experiments performed on transgenic mice expressing a dominant negative variant of the SK3 subunit (SK3-1B, [24]) that suppresses the expression of all SK channel subtypes.
Gene_expression (expression) of SK in neurons associated with targeted disruption
4) Confidence 0.16 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.26 Pain Relevance 0.04
Pyramidal neurons in the neocortex and in the hippocampal formation display high levels of SK1 and SK2 mRNA [32, 83] and protein [35, 36], while neurons in the basolateral amygdala express all three SK channel subunits [32, 36].
Gene_expression (express) of SK in neurons associated with pyramidal cell and amygdala
5) Confidence 0.16 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.06 Pain Relevance 0.30
Thus, in peripheral vessels, it has been shown that EDHF-mediated responses are abolished by the combined inhibition of both SK and IK channels [178] that are expressed exclusively in endothelial cells [181, 183, 184].
Gene_expression (expressed) of SK in endothelial cells
6) Confidence 0.16 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.15 Pain Relevance 0
Interestingly, at the protein level all three SK subunits are detectable in the SNR [36].
Gene_expression (detectable) of SK in SNR
7) Confidence 0.14 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.50
Another prominent site of expression of SK and IK channels in the brain is the cerebral vasculature, in which the function of these channels has been investigated.
Gene_expression (expression) of SK in vasculature
8) Confidence 0.14 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.17 Pain Relevance 0.05
SK channels and disorders of the dopaminergic system
Gene_expression (channels) of SK
9) Confidence 0.14 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.56 Pain Relevance 0.18
The most specific and potent positive modulator of IK and SK channels characterized so far is NS309, displaying a potency ?
Gene_expression (channels) of SK associated with potency
10) Confidence 0.14 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.14
The biophysical characterization in heterologous expression systems showed the voltage independence of SK and IK channels and a half maximal activation by ?
Gene_expression (channels) of SK
11) Confidence 0.14 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.03
Under recording conditions using concentrations of K+ higher than 100 mM on both sides of the membrane, SK channels display a single channel conductance of ?
Gene_expression (channels) of SK
12) Confidence 0.14 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.04
Overexpression of SK1 and SK2 subunits, as well as the application of 1-EBIO, lead to a selective enhancement of the apamin-sensitive IAHP [93, 94], while this current is strongly reduced in layer 5 pyramidal neurons from transgenic mice expressing a truncated form of the SK3 subunit that acts in a dominant negative fashion and suppresses the expression of all SK and IK channels [94].
Gene_expression (expression) of SK in pyramidal neurons associated with targeted disruption and pyramidal cell
13) Confidence 0.13 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.10 Pain Relevance 0.26
It is, however, clear that Ca2+-dependent K+ channels of the SK and IK type are both expressed in cerebral blood vessels and play a significant role in the regulation of local blood flow [185–188].


Gene_expression (expressed) of SK in blood
14) Confidence 0.06 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.21 Pain Relevance 0.03
Effects of blocking SK channels specifically in microglia could only be studied in vitro because SK channels are also expressed in neurons and astrocytes (see Discussion).
Gene_expression (expressed) of SK in microglia
15) Confidence 0.05 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0 Pain Relevance 0
There are three mammalian SK channels (KCNN1/SK1, KCNN2/SK2, KCNN3/SK3), which are predominantly expressed in the nervous system.
Gene_expression (expressed) of SK in nervous system
16) Confidence 0.05 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0.19 Pain Relevance 0.27
Expression of KCNN/SK channels in microglia

[For all quantitative data, statistical analyses and levels of significance are shown on the bar graphs.]

Gene_expression (Expression) of SK in bar
17) Confidence 0.04 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0 Pain Relevance 0
(i) Transcripts for all three cloned SK channels (KCNN1, KCNN2, KCNN3) are expressed in microglia, but KCNN3 predominates and is the only channel up-regulated in LPS-activated microglia.
Gene_expression (channels) of SK in microglia
18) Confidence 0.04 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0.25 Pain Relevance 0.10
(vi) Blocking microglial SK channels with a high concentration of apamin did not globally inhibit the cells; NF?
Gene_expression (channels) of SK
19) Confidence 0.04 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0.62 Pain Relevance 0.18
qRT-PCR [38] was used to monitor transcript expression of SK channels in cultured microglia, as we have previously done for other ion channels [22,30].
Gene_expression (expression) of SK in microglia
20) Confidence 0.04 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0 Pain Relevance 0

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