Disease relevance of KCNN2

• Distribution of Ca2+-activated K channels, SK2 and SK3, in the normal and Hirschsprung's disease bowel [1].
• Prolonged exposure to hypoxia (1% O(2) for 24 h) selectively decreases Kv1.3 protein levels in Jurkat T cells by 47%, but not Kvbeta2 and SK2 Ca-activated K(+) channel subunit levels [2].
• Mutation in a "tesB-Like" Hydroxyacyl-Coenzyme A-Specific Thioesterase Gene Causes Hyperproduction of Extracellular Polyhydroxyalkanoates by Alcanivorax borkumensis SK2 [3].
• Chimaeric SK2 promoter-GUS fusion constructs were transformed into potato by Agrobacterium tumefaciens-mediated transformation [4].
• We have established a pipeline for the distributed sequencing of Alcanivorax borkumensis SK2, Azoarcus sp. BH72, Clavibacter michiganensis subsp. michiganensis NCPPB382, Sorangium cellulosum So ce56 and Xanthomonas campestris pv. vesicatoria 85-10 [5].

High impact information on KCNN2

• We have identified a Ca 2+ -activated K + channel (SK2) in biliary epithelium that is inhibited by apamin [6].
• In intact liver, immunoflourescence with an antibody to SK2 showed a prominent signal in cholangiocyte plasma membrane [6].
• A. borkumensis SK2 has a streamlined genome with a paucity of mobile genetic elements and energy generation-related genes, but with a plethora of genes accounting for its wide hydrocarbon substrate range and efficient oil-degradation capabilities [7].
• We find that activation of cyclic AMP-dependent protein kinase (PKA) with forskolin (50 mum) causes a dramatic decrease in surface localization of the SK2 channel subunit expressed in COS7 cells due to direct phosphorylation of the SK2 channel subunit [8].
• Mutational analysis identified a single PKA phosphorylation site within the amino-terminal of the SK2 subunit at serine 136 [8].

Chemical compound and disease context of KCNN2

• A novel mutant of the marine oil-degrading bacterium Alcanivorax borkumensis SK2, containing a mini-Tn5 transposon disrupting a "tesB-like" acyl-coenzyme A (CoA) thioesterase gene, was found to hyperproduce polyhydroxyalkanoates (PHA), resulting in the extracellular deposition of this biotechnologically important polymer when grown on alkanes [3].
• To identify the genes responsible for alkane degradation in this organism, two putative genes for alkane hydroxylases were cloned from Alcanivorax borkumensis SK2 [9].

Biological context of KCNN2

• The hSK2 gene is encoded by 8 exons and could be assigned to chromosome 5 (q21.2-q22.1) [10].
• 1. The tissue distribution of small conductance Ca(2+)-activated K(+) channels (SK2 and SK3) was examined in three preparations of the guinea-pig intestine: the taneia caeci and the circular muscle layer of the stomach and proximal colon [11].
• With SK1, only Centrales diatoms were identified, and five diatom strains originating from seawater were detectable with SK2 [12].
• Using a highly selective and sensitive LC-MS/MS approach, here we show that SK1 overexpression, but not SK2, in different primary cells and cultured cell lines results in predominant upregulation of the synthesis of dihydrosphingosine-1-phosphate (DHS1P) compared to S1P [13].
• Thus, our findings suggest that PKA phosphorylation of these three sites is necessary for PKA-mediated reorganization of SK2 surface expression [8].

Anatomical context of KCNN2

• Two small conductance, calcium-activated potassium channels (SK channels), SK2 and SK3, have been shown to contribute to the afterhyperpolarization (AHP) and to shape the firing behavior in neurons for example in the hippocampal formation, the dorsal vagal nucleus, the subthalamic nucleus, and the cerebellum [14].
• Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes [15].
• We recently reported for the first time the functional existence of SK2 (KCa2.2) channels in human and mouse cardiac myocytes [15].
• Northern blot analysis reveals the presence of a 2.5-kilobase hSK2 transcript in Jurkat T cells [10].
• Overexpression of the Src family tyrosine kinase p56(lck) in Jurkat cells, up-regulates SK2 currents by 3-fold [10].

Associations of KCNN2 with chemical compounds

• The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3 [16].
• This study reports the effects of DCEBIO, an intermediate conductance Ca2+-activated K+ channel modulator, and the effects of the recently identified potent SK channel enhancer NS309 on recombinant SK2 channels, neuronal apamin-sensitive AHP currents, and the excitability of CA1 neurons [17].
• PKA phosphorylation studies using the intracellular domains of the SK2 channel subunit expressed as glutathione S-transferase fusion protein constructs showed that both the amino-terminal and carboxyl-terminal regions are PKA substrates in vitro [8].
• No significant changes in SK2 mRNA or protein levels, GABAergic inhibition, glutamate receptor function, input resistance, or action potential parameters were observed after chronic deafferentation [18].

Other interactions of KCNN2

• The strong N-C and N-N interaction was specific for SK3 and could not be observed for SK1 and SK2 [19].
• Analysis of mRNA revealed the expression of hSK1, hSK2, and hIK channels in IGR1 cells [20].
• In addition, we used the polymerase chain reaction to demonstrate the presence of SK2 mRNA in Jurkat T cells, whereas SK3 transcripts encoding the other cloned apamin-sensitive SK channel were not detected [21].

Analytical, diagnostic and therapeutic context of KCNN2

• In the present study, we report the first quantitative analysis of SK1, SK2 and SK3 expression in human brain using TaqMan RT-PCR on a range of human brain and peripheral tissue samples [22].
• We confirmed the presence of a small conductance Ca2+-activated K+ channel subtype (SK2) in human and mouse cardiac myocytes using Western blot analysis and reverse transcription-polymerase chain reaction and have cloned SK2 channels from human atria, mouse atria, and ventricles [23].

References