Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS

Hervieu, Guillaume; Cluderay, Jane E.; Gray, Charles A.; Green, P.J; Ranson, Jennie; Randall, Andrew D.; Meadows, Helen

doi:10.1016/s0306-4522(01)00030-6

Cited by 147 publications

(114 citation statements)

References 41 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…An increase in inhibitory tone could represent a neuroprotective mechanism. Furthermore, some immunohistochemical studies indicate that TREK-1 is predominantly expressed in GABAergic interneurons of the hippocampus, isocortex, thalamus and cerebellum [7,28,33,34] .…”

Section: Discussionmentioning

confidence: 99%

Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1

Zhao

Cao

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim:To study the effects of 3-n-butylphthalide (NBP) on the TREK-1 channel expressed in Chinese hamster ovary (CHO) cells. Methods: Whole-cell patch-clamp recording was used to record TREK-1 channel currents. The effects of varying doses of l-NBP on TREK-1 currents were also observed. Current-clamp recordings were performed to measure the resting membrane potential in TREK-1-transfected CHO (TREK-1/CHO) and wild-type CHO (Wt/CHO) cells. Results: l-NBP (0.01-10 μmol/L) showed concentration-dependent inhibition on TREK-1 currents (IC 50 =0.06±0.03 μmol/L), with a maximum current reduction of 70% at a concentration of 10 μmol/L. l-NBP showed a more potent inhibition on TREK-1 current than d-NBP or dl-NBP. This effect was partially reversed upon washout and was not voltage-dependent. l-NBP 10 μmol/L elevated the membrane potential in TREK-1/CHO cells from -55.3 mV to -42.9 mV. However, it had no effect on the membrane potential of Wt/CHO cells. Conclusion: l-NBP potently inhibited TREK-1 current and elevated the membrane potential, which may contribute to its neuroprotective activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1

Zhao

Cao

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Using an antibody corresponding to residues 5 -21 of human TREK1, Hervieu et al (2001) demonstrated the presence of bands that were 56 kDa and, more predominately, 112 kDa in size. In cells overexpressing TREK1, Maingret et al (2000) used a polyclonal antibody directed against residues 1 -44 and 71 -114 to visualise a band of 84 kDa under non-reducing conditions that subsequently migrated to an apparent molecular mass of 45 kDa under reducing conditions (b-mercaptoethanol).…”

Section: Discussionmentioning

confidence: 99%

Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium

Bai¹,

Bugg²,

Greenwood³

et al. 2005

Reproduction

View full text Add to dashboard Cite

Two-pore domain K 1 channels are an emerging family of K 1 channels that may contribute to setting membrane potential in both electrically excitable and non-excitable cells and, as such, influence cellular function. The human uteroplacental unit contains both excitable (e.g. myometrial) and non-excitable cells, whose function depends upon the activity of K 1 channels.We have therefore investigated the expression of two members of this family, TWIK (two-pore domain weak inward rectifying K 1 channel)-related acid-sensitive K 1 channel (TASK) and TWIK-related K 1 channel (TREK) in human myometrium. Using RT-PCR the mRNA expression of TASK and TREK isoforms was examined in myometrial tissue from pregnant women. mRNAs encoding TASK1, 4 and 5 and TREK1 were detected whereas weak or no signals were observed for TASK2, TASK3 and TREK2. Western blotting for TASK1 gave two bands of approximately 44 and 65 kDa, whereas TREK1 gave bands of approximately 59 and 90 kDa in myometrium from pregnant women. TASK1 and TREK1 immunofluorescence was prominent in intracellular and plasmalemmal locations within myometrial cells. Therefore, we conclude that the human myometrium is a site of expression for the two-pore domain K 1 channel proteins TASK1 and TREK1.Reproduction (

show abstract

“…TREK-1 channels are expressed throughout the CNS (Fink et al, 1996;Hervieu et al, 2001;Talley et al, 2001;Gu et al, 2002) with a complex, species-dependent distribution (see Meadows et al, 2000), but with notable levels of expression in the hippocampus, cerebellum, cerebral cortex (Hervieu et al, 2001) and hypothalamus (Maingret et al, 2000a). TREK-1 channels are regulated by a wide range of physiological and pharmacological mediators.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the human two‐pore domain potassium channel, TREK‐1, by fluoxetine and its metabolite norfluoxetine

Kennard

Chumbley

Ranatunga

et al. 2005

British J Pharmacology

168

159

View full text Add to dashboard Cite

1 Block of the human two-pore domain potassium (2-PK) channel TREK-1 by fluoxetine (Prozac R ) and its active metabolite, norfluoxetine, was investigated using whole-cell patch-clamp recording of currents through recombinant channels in tsA 201 cells. 2 Fluoxetine produced a concentration-dependent inhibition of TREK-1 current that was reversible on wash. The IC 50 for block was 19 mM. Block by fluoxetine was voltage-independent. Fluoxetine (100 mM) produced an 84% inhibition of TREK-1 currents, but only a 31% block of currents through a related 2-PK channel, TASK-3. 3 Norfluoxetine was a more potent inhibitor of TREK-1 currents with an IC 50 of 9 mM. Block by norfluoxetine was also voltage-independent. 4 Truncation of the C-terminus of TREK-1 (D89) resulted in a loss of channel function, which could be restored by intracellular acidification or the mutation E306A. The mutation E306A alone increased basal TREK-1 current and resulted in a loss of the slow phase of TREK-1 activation. 5 Progressive deletion of the C-terminus of TREK-1 had no effect on the inhibition of the channel by fluoxetine. The E306A mutation, on the other hand, reduced the magnitude of fluoxetine inhibition, with 100 mM producing only a 40% inhibition. 6 It is concluded that fluoxetine and norfluoxetine are potent inhibitors of TREK-1. Block of TREK-1 by fluoxetine may have important consequences when the drug is used clinically in the treatment of depression.

show abstract

Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS

Cited by 147 publications

References 41 publications

Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1

Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1

Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium

Inhibition of the human two‐pore domain potassium channel, TREK‐1, by fluoxetine and its metabolite norfluoxetine

Contact Info

Product

Resources

About