Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists

Kang, Dawon; Kim, Gyu Tae; Kim, Eun Jin; La, Jun–Ho; Lee, Jeong Soon; Lee, Eun Shin; Park, Jae Yong; Hong, Seong Geun; Han, Jaehee

doi:10.1016/j.bbrc.2008.01.008

Cited by 45 publications

(68 citation statements)

References 21 publications

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“…oxetine also suggests a minor contribution of TRAAK, since it is considerably less sensitive to this drug than TREK-1 (Heurteaux et al, 2006), and TREK-2 inhibition by fluoxetine has also been reported (Kang et al, 2008). TRAAK homodimers have been reported to be strongly blocked by ruthenium red, whereas TREK-1 was practically insensitive (Czirják and Enyedi, 2002); in mSCG neurones I RIL was unaffected by 10 M RR (supplemental Fig.…”

Section: Molecular Counterpart Of I Rilmentioning

confidence: 66%

“…Because expressed mouse TRAAK channels are inhibited by zinc (Czirják and Enyedi, 2006), these results ruled out a major contribution of TRAAK channels to I RIL . The antidepressant fluoxetine strongly inhibits heterologously expressed TREK-1 channels at concentrations that do not affect TRAAK channels (Kennard et al, 2005;Heurteaux et al, 2006); this drug seems to also inhibit TREK-2 cannels (Kang et al, 2008). In mSCG neurons fixed at Ϫ30 mV, fluoxetine (100 M) induced a clear inward current (Ϫ85.7 Ϯ 11.4 pA; n ϭ 9) and robustly reduced the riluzole-activated current in blockers solutions (30.6 Ϯ 5.2 pA; n ϭ 9, p Ͻ 0.01) (Fig.…”

Section: Trek Channel Modulatorsmentioning

confidence: 99%

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Activation of TREK Currents by the Neuroprotective Agent Riluzole in Mouse Sympathetic Neurons

Cadaveira-Mosquera¹,

Ribeiro²,

Reboreda³

et al. 2011

J. Neurosci.

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ϩ channel) mRNA, and the expression of these three proteins was confirmed by immunocytochemistry in mSCG neurons. I RIL was enhanced by zinc, inhibited by barium and fluoxetine, but unaffected by quinine and ruthenium red, strongly suggesting that it was carried through TREK-1/2 channels. Consistently, a channel with properties identical with the heterologously expressed TREK-2 was recorded in most (75%) cell-attached patches. These results provide the first evidence for the expression of K2P channels in the mammalian autonomic nervous system, and they extend the impact of these channels to the entire nervous system.

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Section: Molecular Counterpart Of I Rilmentioning

confidence: 66%

Section: Trek Channel Modulatorsmentioning

confidence: 99%

Activation of TREK Currents by the Neuroprotective Agent Riluzole in Mouse Sympathetic Neurons

Cadaveira-Mosquera¹,

Ribeiro²,

Reboreda³

et al. 2011

J. Neurosci.

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“…TRESK was activated by 40 -80% via coexpressed M 3 muscarinic receptors in COS-7 cells (150,151). Similar activation was evoked by acetylcholine, glutamate, or histamine, when the regulation of native TRESK current was studied in isolated DRG neurons in cell-attached configuration (151).…”

Section: B Regulation By Ca 2؉ and Protein Interactionsmentioning

confidence: 92%

“…Similar activation was evoked by acetylcholine, glutamate, or histamine, when the regulation of native TRESK current was studied in isolated DRG neurons in cell-attached configuration (151). Although the mechanism of activation has not been examined in COS-7 and DRG cells, this latter experiment also indicated that the effect was not membrane delimited.…”

Section: B Regulation By Ca 2؉ and Protein Interactionsmentioning

confidence: 93%

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Enyedi

Czirják

2010

Physiological Reviews

779

769

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Two-pore domain K+ (K2P) channels give rise to leak (also called background) K+ currents. The well-known role of background K+ currents is to stabilize the negative resting membrane potential and counterbalance depolarization. However, it has become apparent in the past decade (during the detailed examination of the cloned and corresponding native K2P channel types) that this primary hyperpolarizing action is not performed passively. The K2P channels are regulated by a wide variety of voltage-independent factors. Basic physicochemical parameters (e.g., pH, temperature, membrane stretch) and also several intracellular signaling pathways substantially and specifically modulate the different members of the six K2P channel subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). The deep implication in diverse physiological processes, the circumscribed expression pattern of the different channels, and the interesting pharmacological profile brought the K2P channel family into the spotlight. In this review, we focus on the physiological roles of K2P channels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.

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“…At Ϫ60-mV holding potential, the majority of low-voltageactivated T-type Ca 2ϩ channels are inactivated (Perez-Reyes 2003) and thus do not contribute to the currents evoked by Ϫ25-mV depolarization. To further dissect background K ϩ currents through TRESK channels, we bath-applied 30 M lamotrigine (Sigma) while evoking whole cell currents using this pulse protocol (Kang et al 2008;Liu et al 2013;Tulleuda et al 2011).…”

Section: Methodsmentioning

confidence: 99%

Nonmigraine-associated TRESK K⁺ channel variant C110R does not increase the excitability of trigeminal ganglion neurons

Guo

Liu

Ren

et al. 2014

Journal of Neurophysiology

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Guo Z, Liu P, Ren F, Cao YQ. Nonmigraine-associated TRESK K ϩ channel variant C110R does not increase the excitability of trigeminal ganglion neurons. J Neurophysiol 112: 568 -579, 2014. First published May 7, 2014 doi:10.1152/jn.00267.2014.-Recent genetic studies suggest that dysfunction of ion channels and transporters may contribute to migraine pathophysiology. A migraineassociated frameshift mutation in the TWIK-related spinal cord K ϩ (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 ϩ 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.

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Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists

Cited by 45 publications

References 21 publications

Activation of TREK Currents by the Neuroprotective Agent Riluzole in Mouse Sympathetic Neurons

Activation of TREK Currents by the Neuroprotective Agent Riluzole in Mouse Sympathetic Neurons

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Nonmigraine-associated TRESK K⁺ channel variant C110R does not increase the excitability of trigeminal ganglion neurons

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Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists

Cited by 45 publications

References 21 publications

Activation of TREK Currents by the Neuroprotective Agent Riluzole in Mouse Sympathetic Neurons

Activation of TREK Currents by the Neuroprotective Agent Riluzole in Mouse Sympathetic Neurons

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

Nonmigraine-associated TRESK K+ channel variant C110R does not increase the excitability of trigeminal ganglion neurons

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Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Nonmigraine-associated TRESK K⁺ channel variant C110R does not increase the excitability of trigeminal ganglion neurons