Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Naunyn Schmiedebergs Arch Pharmacol
2014 Mar 01;3873:291-300. doi: 10.1007/s00210-013-0945-1.
Show Gene links
Show Anatomy links
Functional characterization of zebrafish K2P18.1 (TRESK) two-pore-domain K+ channels.
Rahm AK
,
Wiedmann F
,
Gierten J
,
Schmidt C
,
Schweizer PA
,
Becker R
,
Katus HA
,
Thomas D
.
???displayArticle.abstract???
The human KCNK18 gene is predominantly expressed in brain, spinal cord, and dorsal root ganglion neurons. Encoded K2P18.1K(+) channels are functionally implicated in migraine, pain and anesthesia. Data delineating the in vivo significance of K2P18.1 are still limited owing to a lack of model systems allowing for rapid, whole organism phenotypic analyses. We hypothesized that zebrafish (Danio rerio) might close this scientific gap. This work was designed to characterize the zebrafish ortholog of K2P18.1 in comparison to human K2P18.1 channels. The complete coding sequence of zKCNK18 was amplified from zebrafish cDNA. Zebrafish KCNK18 expression was assessed by in situ hybridization. Human and zebrafish K2P18.1 currents were functionally analyzed using two-electrode voltage clamp electrophysiology and the Xenopus oocyte expression system. KCNK18 mRNA is expressed in zebrafish brain and eyes. Human and zebrafish K2P18.1 proteins share 32 % identity. Zebrafish K2P18.1 channels mediate K(+)-selective background currents that stabilize the negative resting membrane potential. Functional similarities between human and zK2P18.1 currents include open rectification properties, inhibition by barium, and regulation by signaling molecules protein kinase (PK)C, PKA, and phospholipase C. In contrast to the human ortholog, zK2P18.1 exhibited reduced sensitivity to elevation of intracellular calcium levels by ionomycin and was virtually insensitive to inhibition by quinidine. Zebrafish and human K2P18.1 channels share functional and regulatory properties, indicating that the zebrafish may serve as model to assess K2P18.1 function in vivo. However, distinct differences in K2P18.1 current regulation require careful consideration when zebrafish data are extrapolated to human physiology.
Ackermann,
Zebrafish: a genetic model for vertebrate organogenesis and human disorders.
2003, Pubmed
Ackermann,
Zebrafish: a genetic model for vertebrate organogenesis and human disorders.
2003,
Pubmed
Andres-Enguix,
Functional analysis of missense variants in the TRESK (KCNK18) K channel.
2012,
Pubmed
Bautista,
Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels.
2008,
Pubmed
Chae,
Discrete change in volatile anesthetic sensitivity in mice with inactivated tandem pore potassium ion channel TRESK.
2010,
Pubmed
Czirják,
Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation.
2008,
Pubmed
,
Xenbase
Czirják,
The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin.
2004,
Pubmed
,
Xenbase
Czirják,
TRESK background K(+) channel is inhibited by phosphorylation via two distinct pathways.
2010,
Pubmed
,
Xenbase
Czirják,
Targeting of calcineurin to an NFAT-like docking site is required for the calcium-dependent activation of the background K+ channel, TRESK.
2006,
Pubmed
,
Xenbase
Dobler,
TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones.
2007,
Pubmed
,
Xenbase
Dooley,
Zebrafish: a model system for the study of human disease.
2000,
Pubmed
Enyedi,
Molecular background of leak K+ currents: two-pore domain potassium channels.
2010,
Pubmed
Gates,
A genetic linkage map for zebrafish: comparative analysis and localization of genes and expressed sequences.
1999,
Pubmed
Gierten,
Identification and functional characterization of zebrafish K(2P)10.1 (TREK2) two-pore-domain K(+) channels.
2012,
Pubmed
,
Xenbase
Gierten,
The human cardiac K2P3.1 (TASK-1) potassium leak channel is a molecular target for the class III antiarrhythmic drug amiodarone.
2010,
Pubmed
,
Xenbase
Gierten,
Regulation of two-pore-domain (K2P) potassium leak channels by the tyrosine kinase inhibitor genistein.
2008,
Pubmed
,
Xenbase
Goldstein,
Potassium leak channels and the KCNK family of two-P-domain subunits.
2001,
Pubmed
Hassel,
Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy.
2009,
Pubmed
Jowett,
Whole-mount in situ hybridizations on zebrafish embryos using a mixture of digoxigenin- and fluorescein-labelled probes.
1994,
Pubmed
Kang,
TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons.
2006,
Pubmed
Keshavaprasad,
Species-specific differences in response to anesthetics and other modulators by the K2P channel TRESK.
2005,
Pubmed
Kisselbach,
Enhancement of K2P2.1 (TREK1) background currents expressed in Xenopus oocytes by voltage-gated K+ channel β subunits.
2012,
Pubmed
,
Xenbase
Lafrenière,
Migraine: Role of the TRESK two-pore potassium channel.
2011,
Pubmed
Lafrenière,
A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura.
2010,
Pubmed
Lieschke,
Animal models of human disease: zebrafish swim into view.
2007,
Pubmed
Liu,
Potent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics.
2004,
Pubmed
,
Xenbase
Liu,
Functional analysis of a migraine-associated TRESK K+ channel mutation.
2013,
Pubmed
,
Xenbase
Lopes,
PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels.
2005,
Pubmed
,
Xenbase
Patel,
Properties and modulation of mammalian 2P domain K+ channels.
2001,
Pubmed
Rahm,
PKC-dependent activation of human K(2P) 18.1 K(+) channels.
2012,
Pubmed
,
Xenbase
Sandoz,
Optical probing of a dynamic membrane interaction that regulates the TREK1 channel.
2011,
Pubmed
,
Xenbase
Sandoz,
Optical control of endogenous proteins with a photoswitchable conditional subunit reveals a role for TREK1 in GABA(B) signaling.
2012,
Pubmed
Sano,
A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord.
2003,
Pubmed
Schmidt,
Novel electrophysiological properties of dronedarone: inhibition of human cardiac two-pore-domain potassium (K2P) channels.
2012,
Pubmed
,
Xenbase
Schmidt,
Class I antiarrhythmic drugs inhibit human cardiac two-pore-domain K(+) (K2 ₂p) channels.
2013,
Pubmed
,
Xenbase
Seyler,
TASK1 (K(2P)3.1) K(+) channel inhibition by endothelin-1 is mediated through Rho kinase-dependent phosphorylation.
2012,
Pubmed
,
Xenbase
Shin,
From Zebrafish to human: modular medical models.
2002,
Pubmed
Staudacher,
Alternative splicing determines mRNA translation initiation and function of human K(2P)10.1 K+ channels.
2011,
Pubmed
,
Xenbase
Staudacher,
Carvedilol targets human K2P 3.1 (TASK1) K+ leak channels.
2011,
Pubmed
,
Xenbase
Streit,
A specific two-pore domain potassium channel blocker defines the structure of the TASK-1 open pore.
2011,
Pubmed
,
Xenbase
Thomas,
Alternative translation initiation in rat brain yields K2P2.1 potassium channels permeable to sodium.
2008,
Pubmed
,
Xenbase
Tulleuda,
TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury.
2011,
Pubmed
Yang,
Anesthetic properties of the ketone bodies beta-hydroxybutyric acid and acetone.
2007,
Pubmed
,
Xenbase
Yellen,
Permeation in potassium channels: implications for channel structure.
1987,
Pubmed
