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J Neurophysiol
2014 Aug 01;1123:568-79. doi: 10.1152/jn.00267.2014.
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Nonmigraine-associated TRESK K+ channel variant C110R does not increase the excitability of trigeminal ganglion neurons.
Guo Z
,
Liu P
,
Ren F
.
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Recent genetic studies suggest that dysfunction of ion channels and transporters may contribute to migraine pathophysiology. A migraine-associated frameshift mutation in the TWIK-related spinal cord K+ (TRESK) channel results in nonfunctional channels. Moreover, mutant TRESK subunits exert a dominant-negative effect on whole cell TRESK currents and result in hyperexcitability of small-diameter trigeminal ganglion (TG) neurons, suggesting that mutant TRESK may increase the gain of the neuronal circuit underlying migraine headache. However, the nonmigraine-associated TRESK C110R variant exhibits the same effect on TRESK currents as the mutant subunits in Xenopus oocytes, suggesting that dysfunction of TRESK is not sufficient to cause migraine. Here, we confirmed that the C110R variant formed nonfunctional channels and exerted a dominant-negative effect on TRESK currents in HEK293T cells, similar to the migraine-associated mutant TRESK. To compare the functional consequences of TRESK mutations/variants in a more physiological setting, we expressed the mutant TRESK and the C110R variant in cultured mouse TG neurons and investigated their effects on background K+ currents and neuronal excitability. Both mutant TRESK and the C110R variant reduced the endogenous TRESK currents in TG neurons, but the effect of the C110R variant was significantly smaller. Importantly, only TG neurons expressing mutant TRESK subunits, but not those expressing the C110R variant, exhibited a significant increase in excitability. Thus only the migraine-associated TRESK mutation, but not the C110R variant, reduces the endogenous TRESK currents to a degree that affects TG excitability. Our results support a potential causal relationship between the frameshift TRESK mutation and migraine susceptibility.
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
Aronson,
Superfolder GFP is fluorescent in oxidizing environments when targeted via the Sec translocon.
2011,
Pubmed
Bautista,
Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels.
2008,
Pubmed
Brohawn,
Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel.
2012,
Pubmed
Burstein,
Unitary hypothesis for multiple triggers of the pain and strain of migraine.
2005,
Pubmed
Burstein,
Deconstructing migraine headache into peripheral and central sensitization.
2001,
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 Vries,
Molecular genetics of migraine.
2009,
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
Eising,
Pearls and pitfalls in genetic studies of migraine.
2013,
Pubmed
Enyedi,
TRESK: the lone ranger of two-pore domain potassium channels.
2012,
Pubmed
Fang,
Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression.
2006,
Pubmed
Fioretti,
Trigeminal ganglion neuron subtype-specific alterations of Ca(V)2.1 calcium current and excitability in a Cacna1a mouse model of migraine.
2011,
Pubmed
Goadsby,
Neurobiology of migraine.
2009,
Pubmed
Guo,
Over-expression of TRESK K(+) channels reduces the excitability of trigeminal ganglion nociceptors.
2014,
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
Hullugundi,
A hyperexcitability phenotype in mouse trigeminal sensory neurons expressing the R192Q Cacna1a missense mutation of familial hemiplegic migraine type-1.
2014,
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,
Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists.
2008,
Pubmed
Kang,
TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons.
2006,
Pubmed
Kang,
Functional expression of TRESK-2, a new member of the tandem-pore K+ channel family.
2004,
Pubmed
Lafrenière,
A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura.
2010,
Pubmed
Lawson,
Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea-pig.
1997,
Pubmed
Lennertz,
Physiological basis of tingling paresthesia evoked by hydroxy-alpha-sanshool.
2010,
Pubmed
Levy,
Modulation of dural nociceptor mechanosensitivity by the nitric oxide-cyclic GMP signaling cascade.
2004,
Pubmed
Liu,
Functional analysis of a migraine-associated TRESK K+ channel mutation.
2013,
Pubmed
,
Xenbase
Marsh,
Leak K⁺ channel mRNAs in dorsal root ganglia: relation to inflammation and spontaneous pain behaviour.
2012,
Pubmed
Mathie,
Gating of two pore domain potassium channels.
2010,
Pubmed
Miller,
Crystal structure of the human two-pore domain potassium channel K2P1.
2012,
Pubmed
Perez-Reyes,
Molecular physiology of low-voltage-activated t-type calcium channels.
2003,
Pubmed
Piechotta,
The pore structure and gating mechanism of K2P channels.
2011,
Pubmed
Pietrobon,
Pathophysiology of migraine.
2013,
Pubmed
Plant,
A Role for K2P Channels in the Operation of Somatosensory Nociceptors.
2012,
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
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
Tottene,
Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in Ca(v)2.1 knockin migraine mice.
2009,
Pubmed
Tulleuda,
TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury.
2011,
Pubmed
van den Maagdenberg,
A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.
2004,
Pubmed
Victor,
Migraine prevalence by age and sex in the United States: a life-span study.
2010,
Pubmed
Yan,
pH-evoked dural afferent signaling is mediated by ASIC3 and is sensitized by mast cell mediators.
2013,
Pubmed
Yoo,
Regional expression of the anesthetic-activated potassium channel TRESK in the rat nervous system.
2009,
Pubmed
Zhang,
Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura.
2010,
Pubmed
