INT103171

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Context Info
Confidence 0.51
First Reported 2002
Last Reported 2010
Negated 1
Speculated 2
Reported most in Body
Documents 15
Total Number 17
Disease Relevance 3.60
Pain Relevance 6.25

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

plasma membrane (Slc12a5) intracellular (Slc12a5) transmembrane transport (Slc12a5)
Anatomy Link Frequency
neurons 7
spinal 2
retina 1
cortex 1
dorsal horn 1
Slc12a5 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
gABA 519 100.00 Very High Very High Very High
Hippocampus 118 99.80 Very High Very High Very High
agonist 75 99.80 Very High Very High Very High
Arthritis 5 99.66 Very High Very High Very High
spinal dorsal horn 2 99.28 Very High Very High Very High
bDMF 100 98.84 Very High Very High Very High
Dorsal horn 4 98.84 Very High Very High Very High
Spinal cord 21 98.52 Very High Very High Very High
Glutamate receptor 20 98.52 Very High Very High Very High
Acute pain 1 98.12 Very High Very High Very High
Disease Link Frequency Relevance Heat
Generalized Anxiety Disorder 3 100.00 Very High Very High Very High
Arthritis 5 99.66 Very High Very High Very High
Neurological Disease 11 99.52 Very High Very High Very High
Amnesia 1 99.08 Very High Very High Very High
Cognitive Disorder 11 98.72 Very High Very High Very High
Pain 5 98.12 Very High Very High Very High
Hyperalgesia 14 97.40 Very High Very High Very High
Convulsion 301 96.24 Very High Very High Very High
Nociception 13 95.80 Very High Very High Very High
Diabetes Mellitus 5 94.80 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The GABAAergic agonist muscimol increases KCC2 mRNA in male neurons, via activation of voltage sensitive calcium channels and calcium signaling [79, 80]; in contrast, muscimol decreases KCC2 mRNA in female SNR neurons with hyperpolarizing GABAAergic responses [79].
Positive_regulation (increases) of KCC2 mRNA in neurons associated with calcium channel and agonist
1) Confidence 0.51 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0 Pain Relevance 0.35
Activation of protein kinase A pathway (PKA) pathway, through its effects on protein phosphatases, has been implicated in the activation of KCC2 following high frequency stimulation of PN2-3 rat neurons at the deep cerebellar nuclei [234].
Positive_regulation (activation) of KCC2 in neurons
2) Confidence 0.51 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0.08 Pain Relevance 0.09
On a separate note, Ludwig et al. did not observe any changes in KCC2 immunoreactivity in cultured PN0-1 hippocampal mouse neurons chronically treated with either picrotoxin and the sodium channel inhibitor tetrodotoxin (TTX) or combinations of TTX with glutamate receptor inhibitors, proposing that these are not necessary for the developmental increase in KCC2, in hippocampus [180].
Positive_regulation (increase) of KCC2 in neurons associated with tetrodotoxin, glutamate receptor, sodium channel and hippocampus
3) Confidence 0.51 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0 Pain Relevance 0.61
A number of studies have also investigated the regulation of KCC2 and GABAAergic switch by GABA signaling, showing that depolarizing GABAAergic signaling is a positive drive for the developmental upregulation of KCC2 and switch of GABAA receptors, mediating its effects through activation of voltage-sensitive calcium channels and activation of calcium signaling.
Positive_regulation (upregulation) of KCC2 associated with gaba and calcium channel
4) Confidence 0.51 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0 Pain Relevance 0.22
Using human brain tissue from patients deceased from non-neurological disorders, similar developmental increase in KCC2 over NKCC1 was identified in the cortex postnatally, suggesting that a similar gradient of GABAAergic responses may occur [65].
Positive_regulation (increase) of KCC2 in cortex associated with neurological disease
5) Confidence 0.51 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0.10 Pain Relevance 0.03
Nevertheless it is not necessary, since in its absence the increase in KCC2 and GABAAergic switch still occurs, albeit at a later timepoint.
Positive_regulation (increase) of KCC2
6) Confidence 0.51 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0 Pain Relevance 0.24
We, therefore, investigated expression changes of KCC2 and NKCC1 in the spinal dorsal horn of the rat after the intraplantar injection of formalin as an acute nociceptive stimulus.
Spec (investigated) Positive_regulation (changes) of KCC2 in spinal associated with nociception and spinal dorsal horn
7) Confidence 0.50 Published 2006 Journal Neurosci. Res. Section Abstract Doc Link 17007947 Disease Relevance 0.65 Pain Relevance 0.70
Four weeks after saline or STZ (60mg/kg) injection, animals were sacrificed and the spinal segments L2-L3 were removed and immunoreacted for GABA, GAD and KCC2, or processed for western blotting for KCC2.
Positive_regulation (immunoreacted) of KCC2 in spinal associated with gaba and generalized anxiety disorder
8) Confidence 0.49 Published 2008 Journal Neurosci. Lett. Section Abstract Doc Link 18457921 Disease Relevance 0.65 Pain Relevance 0.56
In situ hybridization revealed that neuron-specific K(+)-Cl(-) cotransporter (KCC2) mRNA was significantly reduced in the DMV after axotomy compared with that in control neurons.
Positive_regulation (reduced) of KCC2 in neuron
9) Confidence 0.47 Published 2002 Journal J. Neurosci. Section Abstract Doc Link 12040048 Disease Relevance 0.07 Pain Relevance 0.27
To test for the specificity of primary antibodies, preadsorption controls were performed for the NKCC1 (N-16) and the KCC2 (R-14) polyclonal antibodies using a 5-fold excess of blocking peptides (0.05 ?
Positive_regulation (performed) of KCC2
10) Confidence 0.46 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.07 Pain Relevance 0.11
The neuron-specific K+ -Cl- cotransporter 2 (KCC2) is necessary for fast synaptic inhibition via maintaining the low intracellular chloride concentration required for the hyperpolarizing actions of GABA via GABA(A) receptors.
Positive_regulation (necessary) of K+ -Cl- cotransporter 2 in neuron associated with gaba
11) Confidence 0.40 Published 2006 Journal Brain Res. Bull. Section Abstract Doc Link 17027780 Disease Relevance 0.20 Pain Relevance 0.50
A possible explanation is that activation of BDNF and GABAAergic signaling during neonatal SE may actually upregulate KCC2 (Fig. 2).
Spec (may) Positive_regulation (upregulate) of KCC2 associated with bdmf
12) Confidence 0.37 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0.75 Pain Relevance 0.17
For instance, in male infantile (PN15) SN neurons, GABAAergic depolarizations increase intracellular calcium, the expression of the phosphorylated form of the transcriptional factor CREB (cAMP responsive element binding protein), as well as the expression of calcium regulated mRNAs, such as KCC2 [79, 80, 82].
Positive_regulation (increase) of KCC2 in neurons
13) Confidence 0.37 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0 Pain Relevance 0.12
signaling downregulates whereas Shc signaling upregulates KCC2 in their system [263].
Positive_regulation (upregulates) of KCC2
14) Confidence 0.34 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0.06 Pain Relevance 0.40
In turtle retina, dark rearing inhibited the developmental increase in KCC2 and prolonged the period of excitatory GABAAergic responses [279].
Positive_regulation (increase) of KCC2 in retina
15) Confidence 0.34 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645547 Disease Relevance 0 Pain Relevance 0.53
In acute arthritis, both NKCC1 and KCC2 mRNA increased in superficial but not deep dorsal horn, and this was accompanied by an increase in protein expression.
Positive_regulation (increased) of KCC2 in dorsal horn associated with dorsal horn and arthritis
16) Confidence 0.11 Published 2004 Journal Neurobiol. Dis. Section Abstract Doc Link 15350966 Disease Relevance 0.88 Pain Relevance 0.85
If either GABA is omitted from the cultures or KCC2 activity is not induced, neurons remain multipolar.
Neg (not) Positive_regulation (induced) of KCC2 in neurons associated with gaba
17) Confidence 0.08 Published 2010 Journal Frontiers in Cellular Neuroscience Section Body Doc Link PMC2859806 Disease Relevance 0.08 Pain Relevance 0.51

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