更新于：2024-05-01
TREK1
potassium two pore domain channel subfamily K member 2
更新于：2024-05-01
基本信息
别名 K2p2.1、KCNK2、Outward rectifying potassium channel protein TREK-1 + [10] |
简介 Does not display channel activity but reduces the channel activity of isoform 1 and isoform 2 and reduces cell surface expression of isoform 2.
Ion channel that contributes to passive transmembrane potassium transport (PubMed:23169818). Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner (PubMed:11319556). In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2. In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity). |
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100 项与 TREK1 相关的临床结果
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100 项与 TREK1 相关的转化医学
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2024-02-12American journal of physiology. Cell physiology
Myometrium infection decreases TREK1 through NHE1 and increases contraction in pregnant mice.
Article
作者: Huihui Yu ; Xingxing Wang ; Ruixian Tian ; Xuan Li ; Chenyi Xu ; Jiajia Fei ; Tengteng Li ; Zongzhi Yin
Intrauterine infection during pregnancy can enhance the uterine contractions. A two-pore K+ channel TREK1 is crucial for maintaining uterine quiescence and reducing contractility, with its properties regulated by pH changes in cell microenvironment. Meanwhile, the sodium hydrogen exchanger 1 (NHE1) plays a pivotal role in modulating cellular pH homeostasis, and its activation increases smooth muscle tension. By establishing an infected mouse model of Escherichia coli (E. coli) and lipopolysaccharide (LPS), we employed Western blotting, RT-qPCR, and immunofluorescence to detect changes of TREK1 and NHE1 expression in the myometrium, and isometric recording measured the uterus contraction. The NHE1 inhibitor cariporide was used to explore to the effect of NHE1 on TREK1. Finally, cell contraction assay and siRNA transfection were performed to clarify the relationship between NHE1 and TREK1 in vitro. We found that the uterine contraction was notably enhanced in infected mice with E. coli and LPS administration. Meanwhile, TREK1 expression was reduced, while NHE1 expression was upregulated in infected mice. Cariporide alleviated the increased uterine contraction and promoted myometrium TREK1 expression in LPS-injected mice. Furthermore, suppression of NHE1 with siRNA transfection inhibited the contractility of uterine smooth muscle cells, and activate the TREK1. Altogether, our findings indicate that infection increases the uterine contraction by down-regulating myometrium TREK1 in mice, and the inhibition of TREK1 is attributed to the activation of NHE1.
2024-01-22American journal of physiology. Lung cellular and molecular physiology
TWO PORE POTASSIUM CHANNEL TREK-1 (K2P2.1) REGULATES NLRP3 INFLAMMASOME ACTIVITY IN MACROPHAGES.
Article
作者: Camille N Immanuel ; Bin Teng ; Brittany E Dong ; Elizabeth M Gordon ; Charlean Luellen ; Benjamin Lopez ; Jeffrey Harding ; Stephania A Cormier ; Elizabeth A Fitzpatrick ; Andreas Schwingshackl ; Christopher M Waters
Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages (AMs) and bone marrow derived macrophages (BMDMs) from wild type (wt) and TREK-1-/- mice, we measured responses to inflammasome priming (using LPS) and activation (LPS +ATP). We measured IL-1β, caspase-1, and NLRP3 via ELISA and western blot. A membrane-permeable potassium indicator was used to measure potassium efflux during ATP exposure, and a fluorescence-based assay was used to assess changes in membrane potential. Inflammasome activation induced by LPS+ATP increased IL-1β secretion from wt AMs, whereas activation was significantly reduced in TREK-1-/- AMs. Priming of BMDMs using LPS was not affected by either genetic deficiency or pharmacological inhibition of TREK-1 with Spadin. Cleavage of caspase-1 following LPS+ATP treatment was significantly reduced in TREK-1-/- BMDMs. The intracellular potassium concentration in LPS primed wt BMDMs was significantly lower compared with TREK-1-/- BMDMs or wt BMDMs treated with Spadin. Conversely, activation of TREK-1 with BL1249 caused a decrease in intracellular potassium in wt BMDMs. Treatment of LPS-primed BMDMs with ATP caused a rapid reduction in intracellular potassium levels, with the largest change observed in TREK-1-/- BMDMs. Intracellular K+ changes were associated with changes in the plasma membrane potential (Em), as evidenced by a more depolarized Em in TREK-1-/- BMDMs compared with wt, and Em hyperpolarization upon TREK-1 channel opening with BL1249. These results suggest that TREK-1 is an important regulator of NLRP3 inflammasome activation in macrophages.
2024-01-02Biomacromolecules
Impact of Molecular Dynamics of Polyrotaxanes on Chondrocytes in Double-Network Supramolecular Hydrogels under Physiological Thermomechanical Stimulation.
Article
作者: Theofanis Stampoultzis ; Vijay Kumar Rana ; Yanheng Guo ; Dominique P Pioletti
Hyaline cartilage, a soft tissue enriched with a dynamic extracellular matrix, manifests as a supramolecular system within load-bearing joints. At the same time, the challenge of cartilage repair through tissue engineering lies in replicating intricate cellular-matrix interactions. This study attempts to investigate chondrocyte responses within double-network supramolecular hybrid hydrogels tailored to mimic the dynamic molecular nature of hyaline cartilage. To this end, we infused noncovalent host-guest polyrotaxanes, by blending α-cyclodextrins as host molecules and polyethylene glycol as guests, into a gelatin-based covalent matrix, thereby enhancing its dynamic characteristics. Subsequently, chondrocytes were seeded into these hydrogels to systematically probe the effects of two concentrations of the introduced polyrotaxanes (instilling different levels of supramolecular dynamism in the hydrogel systems) on the cellular responsiveness. Our findings unveiled an augmented level of cellular mechanosensitivity for supramolecular hydrogels compared to pure covalent-based systems. This is demonstrated by an increased mRNA expression of ion channels (TREK1, TRPV4, and PIEZO1), signaling molecules (SOX9) and matrix-remodeling enzymes (LOXL2). Such outcomes were further elevated upon external application of biomimetic thermomechanical loading, which brought a stark increase in the accumulation of sulfated glycosaminoglycans and collagen. Overall, we found that matrix adaptability plays a pivotal role in modulating chondrocyte responses within double-network supramolecular hydrogels. These findings hold the potential for advancing cartilage engineering within load-bearing joints.
2023-12-27
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