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.
Functional analysis of a migraine-associated TRESK K+ channel mutation.
Liu P
,
Xiao Z
,
Ren F
,
Guo Z
,
Chen Z
,
Zhao H
,
Cao YQ
.
???displayArticle.abstract???
Recent genetic and functional studies suggest that migraine may result from abnormal activities of ion channels and transporters. A frameshift mutation in the human TWIK-related spinal cord K(+) (TRESK) channel has been identified in migraine with aura patients in a large pedigree. In Xenopus oocytes, mutant TRESK subunits exert a dominant-negative effect on whole-cell TRESK currents. However, questions remain as to whether and how mutant TRESK subunits affect the membrane properties and the excitability of neurons in the migraine circuit. Here, we investigated the functional consequences of the mutant TRESK subunits in HEK293T cells and mouse trigeminal ganglion (TG) neurons. First, we found that mutant TRESK subunits exhibited dominant-negative effects not only on the size of the whole-cell TRESK currents, but also on the level of TRESK channels on the plasma membrane in HEK293T cells. This likely resulted from the heterodimerization of wild-type and mutant TRESK subunits. Next, we expressed mutant TRESK subunits in cultured TG neurons and observed a significant decrease in the lamotrigine-sensitive K(+) current, suggesting that the mutant TRESK subunits have a dominant-negative effect on currents through the endogenous TRESK channels. Current-clamp recordings showed that neurons expressing mutant TRESK subunits had a higher input resistance, a lower current threshold for action potential initiation, and a higher spike frequency in response to suprathreshold stimuli, indicating that the mutation resulted in hyperexcitability of TG neurons. Our results suggest a possible mechanism through which the TRESK mutation increases the susceptibility of migraine headache.
Andres-Enguix,
Functional analysis of missense variants in the TRESK (KCNK18) K channel.
2012, Pubmed
Andres-Enguix,
Functional analysis of missense variants in the TRESK (KCNK18) K channel.
2012,
Pubmed
Barrett,
Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel.
2005,
Pubmed
Bautista,
Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels.
2008,
Pubmed
Bove,
Primary afferent neurons innervating guinea pig dura.
1997,
Pubmed
Brohawn,
Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel.
2012,
Pubmed
Burstein,
Deconstructing migraine headache into peripheral and central sensitization.
2001,
Pubmed
Cao,
Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy.
2004,
Pubmed
Cavanaugh,
Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli.
2009,
Pubmed
Choi,
Differential slow inactivation and use-dependent inhibition of Nav1.8 channels contribute to distinct firing properties in IB4+ and IB4- DRG neurons.
2007,
Pubmed
De Fusco,
Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.
2003,
Pubmed
Dichgans,
Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine.
,
Pubmed
Dobler,
TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones.
2007,
Pubmed
,
Xenbase
Egenberger,
N-linked glycosylation determines cell surface expression of two-pore-domain K+ channel TRESK.
2010,
Pubmed
,
Xenbase
Enyedi,
TRESK: the lone ranger of two-pore domain potassium channels.
2012,
Pubmed
Enyedi,
Molecular background of leak K+ currents: two-pore domain potassium channels.
2010,
Pubmed
Harper,
Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurones.
1985,
Pubmed
Harper,
Electrical properties of rat dorsal root ganglion neurones with different peripheral nerve conduction velocities.
1985,
Pubmed
Harriott,
Electrophysiological properties of dural afferents in the absence and presence of inflammatory mediators.
2009,
Pubmed
Ho,
CGRP and its receptors provide new insights into migraine pathophysiology.
2010,
Pubmed
Honoré,
The neuronal background K2P channels: focus on TREK1.
2007,
Pubmed
Huang,
Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura.
2012,
Pubmed
Jeng,
Dominant-negative effects of episodic ataxia type 2 mutations involve disruption of membrane trafficking of human P/Q-type Ca2+ channels.
2008,
Pubmed
,
Xenbase
Kang,
Functional expression of TRESK-2, a new member of the tandem-pore K+ channel family.
2004,
Pubmed
Kang,
TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons.
2006,
Pubmed
Kang,
Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists.
2008,
Pubmed
Kim,
Identification of blocker binding site in mouse TRESK by molecular modeling and mutational studies.
2013,
Pubmed
Lafrenière,
Identification of novel genes involved in migraine.
2012,
Pubmed
Lafrenière,
A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura.
2010,
Pubmed
Lafrenière,
Migraine: Role of the TRESK two-pore potassium channel.
2011,
Pubmed
Lawson,
Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea-pig.
1997,
Pubmed
Lesage,
Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.
1996,
Pubmed
,
Xenbase
Li,
The functional organization of cutaneous low-threshold mechanosensory neurons.
2011,
Pubmed
Marsh,
Leak K⁺ channel mRNAs in dorsal root ganglia: relation to inflammation and spontaneous pain behaviour.
2012,
Pubmed
Miller,
Crystal structure of the human two-pore domain potassium channel K2P1.
2012,
Pubmed
Ophoff,
Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4.
1996,
Pubmed
Perez-Reyes,
Molecular physiology of low-voltage-activated t-type calcium channels.
2003,
Pubmed
Plant,
A Role for K2P Channels in the Operation of Somatosensory Nociceptors.
2012,
Pubmed
Pumpens,
HBV core particles as a carrier for B cell/T cell epitopes.
2001,
Pubmed
Rahm,
PKC-dependent activation of human K(2P) 18.1 K(+) channels.
2012,
Pubmed
,
Xenbase
Ruan,
Changes in P2X3 purinoceptors in sensory ganglia of the mouse during embryonic and postnatal development.
2004,
Pubmed
Sano,
A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord.
2003,
Pubmed
Scherrer,
Dissociation of the opioid receptor mechanisms that control mechanical and heat pain.
2009,
Pubmed
Seal,
Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors.
2009,
Pubmed
Snider,
Tackling pain at the source: new ideas about nociceptors.
1998,
Pubmed
Staikopoulos,
Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons.
2007,
Pubmed
Strassman,
Sensitization of meningeal sensory neurons and the origin of headaches.
1996,
Pubmed
Stucky,
Isolectin B(4)-positive and -negative nociceptors are functionally distinct.
1999,
Pubmed
Tao,
Effects of familial hemiplegic migraine type 1 mutation T666M on voltage-gated calcium channel activities in trigeminal ganglion neurons.
2012,
Pubmed
Tulleuda,
TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury.
2011,
Pubmed
Victor,
Migraine prevalence by age and sex in the United States: a life-span study.
2010,
Pubmed
Yan,
Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache.
2011,
Pubmed
Yoo,
Regional expression of the anesthetic-activated potassium channel TRESK in the rat nervous system.
2009,
Pubmed
Zhou,
TRESK gene recombinant adenovirus vector inhibits capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons.
2012,
Pubmed
