INT64873

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Context Info
Confidence 0.38
First Reported 1996
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 17
Total Number 18
Disease Relevance 3.57
Pain Relevance 2.60

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 2
dopaminergic neurons 2
SkBF 2
spike 1
colon 1
SK (Mus musculus)
Pain Link Frequency Relevance Heat
noradrenaline 2 99.58 Very High Very High Very High
Action potential 264 99.36 Very High Very High Very High
nMDA receptor 117 98.00 Very High Very High Very High
long-term potentiation 104 96.56 Very High Very High Very High
Pyramidal cell 260 96.12 Very High Very High Very High
cINOD 1 96.12 Very High Very High Very High
Dopamine 91 94.96 High High
Substantia nigra 93 94.00 High High
Thalamus 15 93.64 High High
Inflammation 36 92.84 High High
Disease Link Frequency Relevance Heat
Colitis 3 99.26 Very High Very High Very High
Arthritis 16 99.06 Very High Very High Very High
Disease 110 98.36 Very High Very High Very High
Colon Cancer 3 98.36 Very High Very High Very High
INFLAMMATION 39 95.88 Very High Very High Very High
Cancer 8 87.12 High High
Increased Venous Pressure Under Development 32 86.24 High High
Manic Depressive Disorder 52 80.96 Quite High
Schizophrenia 188 79.28 Quite High
Sprains And Strains 15 79.12 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We have recently shown that SK inhibitors suppress colitis and hypothesize here that the novel SK inhibitor, ABC294640, prevents the development of colon cancer.
Negative_regulation (inhibitor) of SK in colon associated with colitis and colon cancer
1) Confidence 0.38 Published 2010 Journal Carcinogenesis Section Abstract Doc Link 20688834 Disease Relevance 1.18 Pain Relevance 0.23
Additionally, inhibition of SK channels leads to a shortening of burst duration, an increase in burst frequency and in the intraburst frequency of action potentials [157].
Negative_regulation (inhibition) of SK associated with action potential
2) Confidence 0.12 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.08 Pain Relevance 0.07
Most DCN neurons fire in a single-spiking mode [82, 163, 166]: inhibition of SK channels by apamin leads to a reduction in the post-spike AHP and an increase in the tonic firing frequency [82, 163].
Negative_regulation (inhibition) of SK in spike
3) Confidence 0.12 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.10
In these neurons, inhibition of SK channels by apamin leads to a faster steady firing rate and an increased instantaneous firing rate, due to a reduction in the extent of the membrane potential repolarization during the interspike intervals [87, 88].
Negative_regulation (inhibition) of SK in neurons
4) Confidence 0.12 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.27
Moreover, all three SK channel subtypes are also blocked by a number of organic compounds (curare, quaternary salts of bicuculline, dequalinium, N-methyl-laudanosine, UCL 1684 and UCL 1848) (Table 1, for reviews see also [2, 7]).
Negative_regulation (blocked) of SK
5) Confidence 0.10 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0
The selective blocker apamin, SK enhancers and mice lacking specific SK channel subunits have revealed multifaceted functions of these channels in neurons, glia and cerebral blood vessels.
Negative_regulation (lacking) of SK in blood vessels
6) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Abstract Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.15
At para-physiological temperatures, SK channel inhibition further favors a transition to a burst-firing mode [163, 165], as observed also in Purkinje cells [157].
Negative_regulation (inhibition) of SK in Purkinje cells
7) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.10
Finally, a recent study showed that sigma-1 receptor activation leads to the inhibition of SK channel activity, resulting in a potentiation of NMDA receptor-mediated currents and LTP in CA1 pyramidal neurons [118].
Negative_regulation (inhibition) of SK in pyramidal neurons associated with pyramidal cell, nmda receptor and long-term potentiation
8) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.32
This results in a reduction of SK channel activity and a faster deactivation of SK-mediated currents [114, 115].
Negative_regulation (reduction) of SK
9) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.08 Pain Relevance 0.28
In the case of Parkinson’s disease, for example, two possible strategies can be envisaged: the inhibition of SK3 channels to favor burst firing and consequently an enhanced release of dopamine from the residual dopaminergic neurons that might lead to an alleviation of the symptoms (see also [2]); or the blockade of SK3 channels in an early phase of the disease to slow down the degeneration of dopaminergic neurons, as it has been shown that SK channel inhibition, by increasing excitability and activity of dopaminergic neurons, facilitates their survival in vitro [206].


Negative_regulation (inhibition) of SK in dopaminergic neurons associated with dopamine and disease
10) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.66 Pain Relevance 0.15
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].
Negative_regulation (inhibition) of SK in endothelial cells
11) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.15 Pain Relevance 0
While some in vitro studies have proposed that SK channel inhibition is per se sufficient to switch the firing mode of dopaminergic neurons from single spiking to bursting [138–141], others have failed to observe burst firing in response to the application of SK channel blockers alone [120, 142, 143].
Negative_regulation (inhibition) of SK in dopaminergic neurons
12) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.21
potently displace 125I-labeled apamin binding [51–56], but show little or no block of SK channel-mediated currents [57].
Negative_regulation (block) of SK
13) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0
Thus, inhibition of N-type Ca2+ channels leads to a reduction in the SK-mediated mAHP following action potentials and to burst firing.
Negative_regulation (reduction) of SK-mediated associated with action potential
14) Confidence 0.09 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.12
Microglia stimulation, with and without SK blockers
Neg (without) Negative_regulation (blockers) of SK in Microglia
15) Confidence 0.03 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0.13 Pain Relevance 0
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).
Negative_regulation (blocking) of SK in microglia
16) Confidence 0.03 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0 Pain Relevance 0
In contrast to the abnormal responsiveness of CPRs, the intra-arterial injection of noradrenaline caused the expected decrease in SkBF in all animals tested, and in no instances increases in SkBF were observed.
Negative_regulation (decrease) of SkBF in SkBF associated with noradrenaline
17) Confidence 0.01 Published 1996 Journal J. Auton. Nerv. Syst. Section Abstract Doc Link 8832516 Disease Relevance 0.67 Pain Relevance 0.28
On the other hand, the sympathetic stimulation in the AA rats caused both increase (n = 15) as well as decrease (n = 11) in SkBF.
Negative_regulation (decrease) of SkBF in SkBF associated with arthritis
18) Confidence 0.01 Published 1996 Journal J. Auton. Nerv. Syst. Section Abstract Doc Link 8832516 Disease Relevance 0.62 Pain Relevance 0.30

General Comments

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