INT150144

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Context Info
Confidence 0.78
First Reported 2005
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 31
Total Number 31
Disease Relevance 7.67
Pain Relevance 4.24

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 (Kcnn3) cytoplasm (Kcnn3)
Anatomy Link Frequency
neurons 6
brain 2
blood vessel 2
uterine 1
Golgi cells 1
Kcnn3 (Mus musculus)
Pain Link Frequency Relevance Heat
Neuronal excitability 79 100.00 Very High Very High Very High
midbrain 100 99.82 Very High Very High Very High
Ventral tegmentum 232 99.66 Very High Very High Very High
amygdala 119 99.58 Very High Very High Very High
Pyramidal cell 464 99.56 Very High Very High Very High
Dismenorea 9 98.56 Very High Very High Very High
monoamine 23 98.36 Very High Very High Very High
Substantia nigra 161 96.88 Very High Very High Very High
Hippocampus 104 96.00 Very High Very High Very High
long-term potentiation 196 94.80 High High
Disease Link Frequency Relevance Heat
Schizophrenia 328 100.00 Very High Very High Very High
Manic Depressive Disorder 94 100.00 Very High Very High Very High
Targeted Disruption 82 100.00 Very High Very High Very High
Disease 204 99.80 Very High Very High Very High
Dysmenorrhea 9 98.56 Very High Very High Very High
Pre-term Labor 4 97.96 Very High Very High Very High
Drug Induced Neurotoxicity 23 97.12 Very High Very High Very High
Anorexia 71 92.96 High High
Hyperemia 23 88.44 High High
Anxiety Disorder 31 87.88 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Based on these findings, we hypothesized that SK3 channel expression must be downregulated late in pregnancy to enable the uterus to produce the forceful contractions required for parturition.
Gene_expression (expression) of SK3 in uterus
1) Confidence 0.78 Published 2008 Journal Biol. Reprod. Section Abstract Doc Link 18305226 Disease Relevance 0.22 Pain Relevance 0
SK3-overexpressing mice, by contrast, exhibited lower intrauterine pressure over the same period.
Gene_expression (overexpressing) of SK3 associated with dismenorea
2) Confidence 0.75 Published 2010 Journal Physiol. Genomics Section Abstract Doc Link 20460604 Disease Relevance 0.40 Pain Relevance 0.42
Dopaminergic midbrain neurons express high levels of SK3 mRNA [32, 34, 119] and protein [120].
Gene_expression (express) of SK3 in neurons associated with midbrain
3) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.31
Two subunits leading to the formation of channels highly (SK2) or less sensitive (SK3) to apamin are expressed in subthalamic neurons [32, 36].
Gene_expression (expressed) of SK3 in neurons
4) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.17
Finally, a rare frameshift mutation has been identified in one schizophrenic patient [231], leading to the expression of a truncated SK3 channel comprising the amino-terminal region but missing the transmembrane domains.
Gene_expression (expression) of SK3 associated with schizophrenia
5) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.72 Pain Relevance 0
Although the relative contribution of each of these mechanisms and their possible interplay are still somewhat controversial and might depend on the type of blood vessel and stimulation, a considerable consensus has been reached that the initial step of EDHF-dependent relaxation is the activation of SK (in particular SK3) and IK channels in the endothelium (reviewed in [177–179]), as supported also by findings in genetically modified mice overexpressing or lacking SK3 [181] or lacking IK channels [182].
Gene_expression (overexpressing) of SK3 in blood vessel
6) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.12 Pain Relevance 0
In transgenic mouse lines, SK3-1B was only detected in DCN neurons within the cerebellum and consequently suppressed all SK-mediated currents in these neurons.
Gene_expression (detected) of SK3-1B in cerebellum associated with targeted disruption
7) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.27 Pain Relevance 0.04
Detection of RNA by Northern analysis, in situ hybridization or RT-PCR analysis and protein by immunohistochemistry have revealed that SK1, SK2, and SK3 channels are expressed in the central (CNS) and peripheral (PNS) nervous system [18, 31–38], while IK seems not to be present in central neurons, but is expressed in blood and epithelial cells [19–21, 39], and in peripheral sensory, sympathetic and enteric neurons [37, 38, 40–43].
Gene_expression (expressed) of SK3 in nervous system
8) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.04
In particular, SK3 channel expression has been shown by light and electron microscopy in astrocytes of the supraoptic nucleus and, at lower expression levels, of the substantia nigra pars compacta in adult rat and mouse brain [167], and in olfactory ensheathing glial cells [168].
Gene_expression (expression) of SK3 in astrocytes associated with substantia nigra
9) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.21 Pain Relevance 0.07
However, the expression of SK3 has been reported to increase with age in the hippocampal formation and correlate with age-dependent deficits in synaptic plasticity and hippocampus-dependent learning [86].
Gene_expression (expression) of SK3 in hippocampus associated with hippocampus
10) Confidence 0.74 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.27
Thus, we investigated the effects of SK3 channel expression on gestation and parturition, comparing SK3(T/T) mice to wild type (WT) mice.
Gene_expression (expression) of SK3
11) Confidence 0.68 Published 2008 Journal Biol. Reprod. Section Abstract Doc Link 18305226 Disease Relevance 0.23 Pain Relevance 0
In a previous study, the overexpression of small conductance calcium-activated K(+) channel isoform 3 in transgenic mice, Kcnn3(tm1Jpad)/Kcnn3(tm1Jpad) (also known as SK3(T/T)), led to compromised parturition, which indicates that KCNN3 (also known as SK3) plays an important role in the delivery process.
Gene_expression (overexpression) of Kcnn3 associated with targeted disruption
12) Confidence 0.68 Published 2008 Journal Biol. Reprod. Section Abstract Doc Link 18305226 Disease Relevance 0.17 Pain Relevance 0
The same factors that prompted the investigations on the possible genetic links between KCNN3 and schizophrenia or bipolar disorder (physiological role of SK3 in neurons, expression pattern of SK3 in brain, polymorphic CAG-repeats in the SK3 amino-terminal region and chromosomal localization of the SK3 gene; see above) led also to studies on its possible involvement in anorexia.
Gene_expression (expression) of SK3 in brain associated with manic depressive disorder, anorexia and schizophrenia
13) Confidence 0.65 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.86 Pain Relevance 0
Golgi cells express high levels of the SK3 subunit [32].
Gene_expression (express) of SK3 subunit in Golgi cells
14) Confidence 0.65 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.08
The SK channels responsible for these effects are most likely formed by SK1 and SK2 subunits, while no [32, 82] or only weak [36] SK3 expression was detected in the DCN.
Gene_expression (expression) of SK3
15) Confidence 0.65 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.17 Pain Relevance 0.07
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 (expressing) of SK3-1B in neurons associated with targeted disruption
16) Confidence 0.64 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.26 Pain Relevance 0.04
In situ hybridization and immunohistochemistry studies on brain tissue from adult rat and mouse have shown further that the SK1, SK2 and SK3 channel subunits have partially overlapping but clearly distinct distribution patterns, with SK1 and SK2 frequently expressed in the same neurons, and SK3 presenting a complementary distribution [32, 34–36].
Gene_expression (expressed) of SK3 in neurons
17) Confidence 0.64 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.07
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 (expressing) of SK3 subunit in neurons associated with targeted disruption
18) Confidence 0.64 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.26 Pain Relevance 0.04
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 SK3 in microglial cells
19) Confidence 0.58 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0.10 Pain Relevance 0.07
The apparent discrepancy between the strong effect of SK channel blockers in vivo and their lack of effect in vitro on the firing pattern of VTA neurons might be due to the presence of a pronounced gradient in the expression of SK3 channel subunits.
Gene_expression (expression) of SK3 in neurons associated with ventral tegmentum
20) Confidence 0.58 Published 2008 Journal Cell Mol Life Sci Section Body Doc Link PMC2798969 Disease Relevance 0 Pain Relevance 0.53

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