High impact information on KCNK10

• However, the most similar channel is TREK-2 (two-pore domain K+ channel), and TRESK also has two pore-forming domains and four transmembrane domains that are evolutionarily conserved in the two-pore domain K+ channel family [1].
• This channel, called TREK2, is closely related to TREK1 (78% of homology) [2].
• TREK2 is abundantly expressed in pancreas and kidney and to a lower level in brain, testis, colon, and small intestine [2].
• In the central nervous system, TREK2 has a widespread distribution with the highest levels of expression in cerebellum, occipital lobe, putamen, and thalamus [2].
• As with TREK1, TREK2 is activated by the volatile general anesthetics chloroform, halothane, and isoflurane and by the neuroprotective agent riluzole [2].

Biological context of KCNK10

• Our results suggest that alternative splicing of TREK-2 contributes to the diversity of two-pore-domain K+ channels [3].
• Two novel alternatively spliced isoforms of the human two-pore-domain potassium channel TREK-2 were isolated from cDNA libraries of human kidney and fetal brain [3].
• These results suggest that the agonist-induced inhibition of TREK-2 via M(3) receptor occurs primarily via PKC-mediated phosphorylation [4].
• Thus, the C-terminus endows TREK-2 with unique channel kinetics and the ability to be gated by free fatty acids and low pHi, and with increased mechanosensitivity [5].

Anatomical context of KCNK10

• Expression of TREK-2 in COS-7 cells induced a time-independent and non-inactivating K(+)-selective current [6].
• Unlike TREK-1, whose mRNA has been reported to be expressed in many different tissues, TREK-2 mRNA is expressed mainly in the cerebellum, spleen, and testis as judged by reverse transcriptase-polymerase chain reaction and Northern blot analysis [6].
• In the present study, the effects of divalent metal ions (Ba(2+), Co(2+), Ni(2+), Pb(2+), and Zn(2+)) were examined on TREK-2 expressed in Xenopus oocytes using the two-electrode voltage clamping technique [7].
• Trek-1 but not TREK-2 was expressed in both pregnant and non-pregnant myometrium [8].

Associations of KCNK10 with chemical compounds

• TREK-2 was also activated by arachidonic acid and other naturally occurring unsaturated free fatty acids [6].
• TREK-2 was partially blocked (36%) by 2 mm Ba(2+) [6].
• The H2O2-induced activation of TREK-2 currents was also observed at single channel levels in cell-attached patches, and the effect was reversed by the reducing agent, dithiothreitol [9].
• Furthermore, direct application of 5,5'-dithiobis-(2-nitrobenzoic acid) inhibited TREK-2, suggesting that the H2O2-induced activation does not result from direct oxidation of TREK-2 proteins [9].
• Hydrogen peroxide selectively increases TREK-2 currents via myosin light chain kinases [9].

Other interactions of KCNK10

• TREK-1 and TRAAK mRNA expression was predominantly CNS specific in contrast to the closely related TREK-2, which was expressed in both CNS and peripheral tissues [10].
• Pretreatment of cells with a protein kinase C inhibitor (bisindolylmaleimide, 10 muM) markedly inhibited ACh-induced inhibition of TREK-2 [4].

References