Disease relevance of KCNK9

• Altered expression of KCNK9 in colorectal cancers [1].
• Statistically, KCNK9 protein expression was not related to tumor stage (Bartholomew test, p>0.05) and lymph node metastasis (Chi-Square test, p=0.8338) [1].
• Sequencing of the KCNK9 gene in the genetic absence epilepsy rats from Strasbourg (GAERS), a well established genetic model of this disease, reveals an additional alanine residue in a polyalanine tract within the C-terminal intracellular domain [2].
• 3. We examined a series of breast cancer samples harboring amplification of this region and determined that KCNK9 is the sole overexpressed gene within the amplification epicenter [3].
• Overexpression of KCNK9 in cell lines promotes tumor formation and confers resistance to both hypoxia and serum deprivation, suggesting that its amplification and overexpression plays a physiologically important role in human breast cancer [3].

Psychiatry related information on KCNK9

• However, Dauncey reported impairment of a relatively simple reaction time task 3 hr after a dose of alcohol, when the blood alcohol concentration was at or near 0 [4].

High impact information on KCNK9

• In this report, we demonstrate that a point mutation (G95E) within the consensus K+ filter of TASK3 not only abolished TASK3 potassium channel activity but also abrogated its oncogenic functions, including proliferation in low serum, resistance to apoptosis, and promotion of tumor growth [5].
• TASK3 gene (Kcnk9) is amplified and overexpressed in several types of human carcinomas [5].
• TASK-1 and TASK-3, members of the two-pore-domain channel family, are widely expressed leak potassium channels responsible for maintenance of cell membrane potential and input resistance [6].
• Finally, we have used Zn(2+) treatment as a maneuver able to discriminate between these two homologues of hTASK and show that the most likely candidate channel for O(2) sensing in these cells is hTASK3 [7].
• Expression of TASK-3 in Xenopus oocytes revealed an outwardly rectifying K(+) current that was strongly decreased in the presence of lower extracellular pH [8].

Chemical compound and disease context of KCNK9

• Acidic pH values and hypoxia inhibit TASK-1 and TASK-3 channel function, and halothane enhances this function [9].
• Furthermore, we have used antisense oligodeoxynucleotides directed against hTASK1 and hTASK3 to suppress almost completely the hTASK1 protein and show that these cells no longer respond to acute hypoxia; this behavior was not mirrored in liposome-only or missense-treated cells [7].

Biological context of KCNK9

• When Xenopus oocytes were injected with KT3.2 cRNA, the resting membrane potential was brought close to the potassium equilibrium potential [10].
• The KT3.2 gene is located at chromosome 8q24 1-3, and the KT3.3 gene maps to chromosome 20q13.1 [10].
• For TREK1, TASK1 and TASK3 channels, PIP2 hydrolysis underlies inhibition by several agonists [11].
• These results provide a more finely detailed picture of TASK-3 expression and indicate a role for TASK-3 in modulating cerebral synaptic transmission and responses to CNS active drugs [12].
• We have named the channel TASK-5 owing to its sequence homology with TASK-1 and TASK-3 [13].

Anatomical context of KCNK9

• Deletion of a single amino acid at the C-terminal end of TASK-1 or TASK-3 abolished binding of 14-3-3 and strongly reduced the macroscopic currents observed in Xenopus oocytes [14].
• Purkinje cells were strongly stained and granule cells and astrocytes were moderately positive for TASK-3 [15].
• The TASK-3 labelling was stronger in general, but it was particularly intense in the Purkinje cells and pia mater [15].
• The pia mater, astrocytes, Purkinje and granule cells demonstrated strong TASK-1 and TASK-3 positivities [15].
• Doxapram stimulates ventilation through an effect on carotid bodies, and we hypothesized that stimulation might result from inhibition of TASK-1 or TASK-3 K channel function [9].

Associations of KCNK9 with chemical compounds

• Ruthenium red inhibits TASK-3 potassium channel by interconnecting glutamate 70 of the two subunits [16].
• For TASK-3, mutation of histidine 98 to aspartate or alanine considerably reduced this effect of pH [17].
• Our data indicate that TASK-1 and TASK-3 do not play a role in mediating the immobility produced by halothane, although they are plausible molecular targets for the ventilatory effects of doxapram [9].
• Moreover, after blocking homomeric TASK-3 channels with ruthenium red, we found a major component of motoneuronal isoflurane-sensitive TASK-like current that could be attributed to heteromeric TASK channels [18].
• TASK-3 was blocked by barium (57%, 3 mM), quinidine (37%, 100 microM), and lidocaine (62%, 1 mM) [19].

Other interactions of KCNK9

• A TASK3 channel (KCNK9) mutation in a genetic model of absence epilepsy [2].
• When two TASK-3 coding sequences were concatenated, and the entire homodimer was expressed as a single polypeptide chain, the resulting tandem channel was also sensitive to RR [16].
• They represented three different levels of language complexity from lowest to highest as follows: task 1, object naming; task 2, sentence completion; and task 3, responsive naming [20].
• Quantitative determination of mRNA expression levels and immunocytochemical staining demonstrated that TASK3 and HCN2 channels represent the dominant thalamic isoforms and are coexpressed in TC neurons [21].
• TRAAK and TASK-3 subunits showed significant decreases at 3 days and 3 weeks following deafness, but these differences were no longer significant at 3 months [22].

Analytical, diagnostic and therapeutic context of KCNK9

• In the present study, we examined the expression and somatic mutations of KCNK9 in 124 colorectal cancers by immunohistochemistry using tissue microarray and PCR-SSCP [1].
• Reverse transcriptase-polymerase chain reaction analysis showed that TASK-3 mRNA is expressed in many rat tissues including brain, kidney, liver, lung, colon, stomach, spleen, testis, and skeletal muscle, and at very low levels in the heart and small intestine [19].
• A comprehensive in situ hybridization analysis revealed that both TASK-1 and TASK-3 transcripts are most strongly expressed in many neurons likely to be cholinergic, serotonergic, or noradrenergic [23].
• Using immunogold electron microscopy TASK-3 was identified at the cell surface associated with synapses and within the intracellular synthetic compartments [12].
• We have shown by radiation hybrid mapping that human TASK-3 can be assigned to chromosome 8q24 [24].

References