Ca2+ Regulation of TRP Ion Channels

Hasan, Raquibul; Zhang, Xuming

doi:10.3390/ijms19041256

Cited by 65 publications

(62 citation statements)

References 130 publications

(213 reference statements)

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“…It is well known that sustained elevation of intracellular Ca 2+ was capable of inducing Ca 2+ entry-dependent ROS production [8], mitochondrial depolarization [9] and then apoptosis [10]. Transient receptor potential (TRP) ion channels are a large family of membrane-associated cation channels, which most permeable to Ca 2+ [11]. Therefore, the activation of TRP channels serves as an important Ca 2+ entry pathway contributing to fluctuation in intracellular Ca 2+ and subsequent signal pathways [12].…”

Section: Introductionmentioning

confidence: 99%

Transient receptor potential ankyrin 1 (trpa1) mediates il-1β-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction

et al. 2018

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BackgroundChondrocyte apoptosis is a central feature in the progression of osteoarthritis (OA), and would be triggered by sustained elevation of intracellular calcium ion (Ca2+), also known as a cellular second messenger. Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, and the activation of which causes an influx of cation ions, in particularly Ca2+, into the activated cells. Therefore, we investigate the potential role of TRPA1 in mediating Ca2+ influx to promote chondrocyte apoptosis in OA.MethodsThe expression of TRPA1 in interleukin (IL)-1β-treated rat chondrocytes was assessed by Polymerase chain reaction (PCR) and Western blot (WB), and the functionality of TRPA1 channel by Ca2+ influx measurements. Meanwhile, the chondrocyte apoptosis in IL-1β-treated cells was measured by TUNEL assay and flow cytometry. The measurement of mitochondrial membrane potential and apoptosis-associated proteins after inhibition of TRPA1 were also performed in IL-1β-treated rat chondrocytes.ResultsAfter being induced by IL-1β, the gene and protein expression of TRPA1 was increased in the dose-dependent manner. Meanwhile, Ca2+ influx mediated by TRPA1 in rat chondrocytes was also enhanced. Pharmacological inhibition of TRPA1 downregulated the apoptotic rate in IL-1β-treated rat chondrocytes. In addition, the membrane potential depolarization was improved and significantly increased expression of apoptosis-associated proteins also reduced by the TRPA1 antagonist.ConclusionsWe found the IL-1β caused the increased functional expression of TRPA1, the activation of which involved IL-1β-induced apoptosis in rat chondrocytes. The potential mechanism may be linked to the intracellular calcium overload mediated by TRPA1 and attendant mitochondrial dysfunction.

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Section: Introductionmentioning

confidence: 99%

Transient receptor potential ankyrin 1 (trpa1) mediates il-1β-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction

et al. 2018

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“…TRP channels are tetramers composed of four subunits that are mostly homomeric but can also be heteromeric 15,29 . Most TRP channels are permeable to calcium and subjected to sophisticated autoregulation mechanisms that self-regulate calcium entry and downstream calcium signaling 30 . We can explain the temporary spastic paralysis of B. malayi by an agonist action of DEC on TRP channels that is followed by auto-regulatory mechanisms leading to a subsequent closure of the TRP channel and recovery of motility.…”

Section: Discussionmentioning

confidence: 99%

Diethylcarbamazine activates TRP channels including TRP-2 in filaria, Brugia malayi

et al. 2020

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Diethylcarbamazine is an important classic drug used for prevention and treatment of lymphatic filariasis and loiasis, diseases caused by filarial nematodes. Despite many studies, its site of action has not been established. Until now, the consensus has been that diethylcarbamazine works by activating host immune systems, not by a direct action on the parasites. Here we show that low concentrations of diethylcarbamazine have direct and rapid (<30 s) temporary spastic paralyzing effects on the parasites that lasts around 4 h, which is produced by diethylcarbamazine opening TRP channels in muscle of Brugia malayi involving TRP-2 (TRPC-like channel subunits). GON-2 and CED-11, TRPM-like channel subunits, also contributed to diethylcarbamazine responses. Opening of these TRP channels produces contraction and subsequent activation of calcium-dependent SLO-1K channels. Recovery from the temporary paralysis is consistent with inactivation of TRP channels. Our observations elucidate mechanisms for the rapid onset and short-lasting therapeutic actions of diethylcarbamazine.

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“…Electrophysiological analyses have disclosed that the shortening of the length of the C-terminal loop increases TRPC3 activity and that the elongation of the length of the loop has the opposite effect. The C-terminal moiety of TRPM4 was proposed to be a target of CaM already in several previous studies [ 1 , 20 , 21 ]. However, all cryo-EM structures of TRPM4 show the re-entrant helix embedded in the membrane—i.e., not readily available for CaM.…”

Section: Discussionmentioning

confidence: 99%

“…The specific positions of hydrophobic amino acids (either 1-5-10 and/or 1-8-14 [ 13 , 17 , 18 , 19 ]) are used for the bioinformatic identification of potential CaM-binding sites [ 17 ]. Indeed, several such binding sites have been proposed in the proximal C-terminal region of TRPM4 [ 12 , 20 , 21 ]. These binding sites seem to be interconnected to each other in a continuous sequence, because a deletion of any region has severely reduced the Ca 2+ sensitivity of the TRPM4 channel [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Mapping of CaM, S100A1 and PIP2-Binding Epitopes in the Intracellular N- and C-Termini of TRPM4

Boušová

Barvı́k

Heřman

et al. 2020

IJMS

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Molecular determinants of the binding of various endogenous modulators to transient receptor potential (TRP) channels are crucial for the understanding of necessary cellular pathways, as well as new paths for rational drug designs. The aim of this study was to characterise interactions between the TRP cation channel subfamily melastatin member 4 (TRPM4) and endogenous intracellular modulators—calcium-binding proteins (calmodulin (CaM) and S100A1) and phosphatidylinositol 4, 5-bisphosphate (PIP2). We have found binding epitopes at the N- and C-termini of TRPM4 shared by CaM, S100A1 and PIP2. The binding affinities of short peptides representing the binding epitopes of N- and C-termini were measured by means of fluorescence anisotropy (FA). The importance of representative basic amino acids and their combinations from both peptides for the binding of endogenous TRPM4 modulators was proved using point alanine-scanning mutagenesis. In silico protein–protein docking of both peptides to CaM and S100A1 and extensive molecular dynamics (MD) simulations enabled the description of key stabilising interactions at the atomic level. Recently solved cryo-Electron Microscopy (EM) structures made it possible to put our findings into the context of the entire TRPM4 channel and to deduce how the binding of these endogenous modulators could allosterically affect the gating of TRPM4. Moreover, both identified binding epitopes seem to be ideally positioned to mediate the involvement of TRPM4 in higher-order hetero-multimeric complexes with important physiological functions.

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Ca2+ Regulation of TRP Ion Channels

Cited by 65 publications

References 130 publications

Transient receptor potential ankyrin 1 (trpa1) mediates il-1β-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction

Transient receptor potential ankyrin 1 (trpa1) mediates il-1β-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction

Diethylcarbamazine activates TRP channels including TRP-2 in filaria, Brugia malayi

Mapping of CaM, S100A1 and PIP2-Binding Epitopes in the Intracellular N- and C-Termini of TRPM4

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