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.
Br J Pharmacol
2012 May 01;1662:764-73. doi: 10.1111/j.1476-5381.2011.01813.x.
Show Gene links
Show Anatomy links
PKC-dependent activation of human K(2P) 18.1 K(+) channels.
Rahm AK
,
Gierten J
,
Kisselbach J
,
Staudacher I
,
Staudacher K
,
Schweizer PA
,
Becker R
,
Katus HA
,
Thomas D
.
???displayArticle.abstract???
Two-pore-domain K(+) channels (K(2P) ) mediate K(+) background currents that modulate the membrane potential of excitable cells. K(2P) 18.1 (TWIK-related spinal cord K(+) channel) provides hyperpolarizing background currents in neurons. Recently, a dominant-negative loss-of-function mutation in K(2P) 18.1 has been implicated in migraine, and activation of K(2P) 18.1 channels was proposed as a therapeutic strategy. Here we elucidated the molecular mechanisms underlying PKC-dependent activation of K(2P) 18.1 currents.Human K(2P) 18.1 channels were heterologously expressed in Xenopus laevis oocytes, and currents were recorded with the two-electrode voltage clamp technique.Stimulation of PKC using phorbol 12-myristate-13-acetate (PMA) activated the hK(2P) 18.1 current by 3.1-fold in a concentration-dependent fashion. The inactive analogue 4α-PMA had no effect on channel activity. The specific PKC inhibitors bisindolylmaleimide I, Ro-32-0432 and chelerythrine reduced PMA-induced channel activation indicating that PKC is involved in this effect of PMA. Selective activation of conventional PKC isoforms with thymeleatoxin (100 nM) did not reproduce K(2P) 18.1 channel activation. Current activation by PMA was not affected by pretreatment with CsA (calcineurin inhibitor) or KT 5720 (PKA inhibitor), ruling out a significant contribution of calcineurin or cross-talk with PKA to the PKC-dependent hK(2P) 18.1 activation. Finally, mutation of putative PKC phosphorylation sites did not prevent PMA-induced K(2P) 18.1 channel activation.We demonstrated that activation of hK(2P) 18.1 (TRESK) by PMA is mediated by PKC stimulation. Hence, PKC-mediated activation of K(2P) 18.1 background currents may serve as a novel molecular target for migraine treatment.
Alexander,
Guide to Receptors and Channels (GRAC), 5th edition.
2011, Pubmed
Alexander,
Guide to Receptors and Channels (GRAC), 5th edition.
2011,
Pubmed
Barros,
Modulation of human erg K+ channel gating by activation of a G protein-coupled receptor and protein kinase C.
1998,
Pubmed
,
Xenbase
Bautista,
Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels.
2008,
Pubmed
Besana,
Activation of protein kinase C epsilon inhibits the two-pore domain K+ channel, TASK-1, inducing repolarization abnormalities in cardiac ventricular myocytes.
2004,
Pubmed
Cain,
mGlu4 potentiation of K(2P)2.1 is dependant on C-terminal dephosphorylation.
2008,
Pubmed
Chae,
Discrete change in volatile anesthetic sensitivity in mice with inactivated tandem pore potassium ion channel TRESK.
2010,
Pubmed
Chen,
Post-transcriptional control of human ether-a-go-go-related gene potassium channel protein by alpha-adrenergic receptor stimulation.
2010,
Pubmed
Czirják,
Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation.
2008,
Pubmed
,
Xenbase
Czirják,
TRESK background K(+) channel is inhibited by phosphorylation via two distinct pathways.
2010,
Pubmed
,
Xenbase
Czirják,
The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin.
2004,
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
Enyedi,
Molecular background of leak K+ currents: two-pore domain potassium channels.
2010,
Pubmed
Fink,
Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel.
1996,
Pubmed
,
Xenbase
Gierten,
Regulation of two-pore-domain (K2P) potassium leak channels by the tyrosine kinase inhibitor genistein.
2008,
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,
Identification and functional characterization of zebrafish K(2P)10.1 (TREK2) two-pore-domain K(+) channels.
2012,
Pubmed
,
Xenbase
Goldstein,
Potassium leak channels and the KCNK family of two-P-domain subunits.
2001,
Pubmed
Gu,
Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2.
2002,
Pubmed
Honoré,
An intracellular proton sensor commands lipid- and mechano-gating of the K(+) channel TREK-1.
2002,
Pubmed
Kang,
Properties of single two-pore domain TREK-2 channels expressed in mammalian cells.
2007,
Pubmed
,
Xenbase
Kang,
TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons.
2006,
Pubmed
Karle,
Human cardiac inwardly-rectifying K+ channel Kir(2.1b) is inhibited by direct protein kinase C-dependent regulation in human isolated cardiomyocytes and in an expression system.
2002,
Pubmed
,
Xenbase
Kathöfer,
Human beta(3)-adrenoreceptors couple to KvLQT1/MinK potassium channels in Xenopus oocytes via protein kinase C phosphorylation of the KvLQT1 protein.
2003,
Pubmed
,
Xenbase
Keshavaprasad,
Species-specific differences in response to anesthetics and other modulators by the K2P channel TRESK.
2005,
Pubmed
Kiehn,
Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels.
1999,
Pubmed
,
Xenbase
Kiesecker,
Regulation of cardiac inwardly rectifying potassium current IK1 and Kir2.x channels by endothelin-1.
2006,
Pubmed
,
Xenbase
Koh,
TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. An essential role in smooth muscle inhibitory neurotransmission.
2001,
Pubmed
Lafrenière,
A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura.
2010,
Pubmed
Liu,
Potent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics.
2004,
Pubmed
,
Xenbase
Maingret,
TREK-1 is a heat-activated background K(+) channel.
2000,
Pubmed
,
Xenbase
Mant,
Protein kinase A is central for forward transport of two-pore domain potassium channels K2P3.1 and K2P9.1.
2011,
Pubmed
,
Xenbase
Murbartián,
Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels.
2005,
Pubmed
Nishizuka,
Turnover of inositol phospholipids and signal transduction.
1984,
Pubmed
Patel,
A mammalian two pore domain mechano-gated S-like K+ channel.
1998,
Pubmed
Ron,
New insights into the regulation of protein kinase C and novel phorbol ester receptors.
1999,
Pubmed
Ryves,
Activation of the PKC-isotypes alpha, beta 1, gamma, delta and epsilon by phorbol esters of different biological activities.
1991,
Pubmed
Sano,
A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord.
2003,
Pubmed
Scherer,
Activation of inwardly rectifying Kir2.x potassium channels by beta 3-adrenoceptors is mediated via different signaling pathways with a predominant role of PKC for Kir2.1 and of PKA for Kir2.2.
2007,
Pubmed
,
Xenbase
Seyler,
TASK1 (K(2P)3.1) K(+) channel inhibition by endothelin-1 is mediated through Rho kinase-dependent phosphorylation.
2012,
Pubmed
,
Xenbase
Skeberdis,
mGluR1-mediated potentiation of NMDA receptors involves a rise in intracellular calcium and activation of protein kinase C.
2001,
Pubmed
,
Xenbase
Smith,
Calcineurin as a nociceptor modulator.
2009,
Pubmed
Staudacher,
Carvedilol targets human K2P 3.1 (TASK1) K+ leak channels.
2011,
Pubmed
,
Xenbase
Staudacher,
Alternative splicing determines mRNA translation initiation and function of human K(2P)10.1 K+ channels.
2011,
Pubmed
,
Xenbase
Thomas,
Alternative translation initiation in rat brain yields K2P2.1 potassium channels permeable to sodium.
2008,
Pubmed
,
Xenbase
Thomas,
Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein.
2003,
Pubmed
,
Xenbase
Thomas,
Activation of cardiac human ether-a-go-go related gene potassium currents is regulated by alpha(1A)-adrenoceptors.
2004,
Pubmed
,
Xenbase
Tulleuda,
TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury.
2011,
Pubmed
Veale,
G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C.
2007,
Pubmed
Vincent,
Dual level of interactions between calcineurin and PKC-epsilon in cardiomyocyte stretch.
2006,
Pubmed
Yang,
Anesthetic properties of the ketone bodies beta-hydroxybutyric acid and acetone.
2007,
Pubmed
,
Xenbase
Zhang,
Aquaporin-1 channel function is positively regulated by protein kinase C.
2007,
Pubmed
,
Xenbase
Zitron,
Kir2.x inward rectifier potassium channels are differentially regulated by adrenergic alpha1A receptors.
2008,
Pubmed
,
Xenbase
