scholarly journals TRPC channels: Dysregulation and Ca2+ Mishandling In Ischemic Heart Disease

2019 ◽  
Author(s):  
Debora Falcon ◽  
Isabel Galeano-Otero ◽  
Marta Martín-Bórnez ◽  
María Fernández-Velasco ◽  
Isabel Gallardo-Castillo ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Cardiac Cells ◽  
Membrane Receptors ◽  
Trpc Channels ◽  
Ischemia And Reperfusion ◽  
Sense And Respond ◽  
Transient Receptor

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP, TRPC may form homo or heterotetrameric ion channel, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase of the expression of different TRPC isoforms has been observed in different animal model of heart infarcts, and in vitro experimental model of ischemia and reperfusion. TRPC-mediated increase of the intracellular Ca2+ concentration seems required for the activation of signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we will highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion, and to heart infarction.

scholarly journals TRPC Channels: Dysregulation and Ca2+ Mishandling in Ischemic Heart Disease

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 173 ◽  
Author(s):  
Débora Falcón ◽  
Isabel Galeano-Otero ◽  
Marta Martín-Bórnez ◽  
María Fernández-Velasco ◽  
Isabel Gallardo-Castillo ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Experimental Models ◽  
Cardiac Cells ◽  
Membrane Receptors ◽  
Trpc Channels ◽  
Ischemia And Reperfusion

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP channels, TRPC channels may form homo or heterotetrameric ion channels, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase in the expression of different TRPC isoforms was observed in different animal models of heart infarcts and in vitro experimental models of ischemia and reperfusion. TRPC channel-mediated increase of the intracellular Ca2+ concentration seems to be required for the activation of the signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion and to heart infarction.

scholarly journals Membrane translocation of TRPC6 channels and endothelial migration are regulated by calmodulin and PI3 kinase activation

2016 ◽  
Vol 113 (8) ◽  
pp. 2110-2115 ◽  
Author(s):  
Pinaki Chaudhuri ◽  
Michael A. Rosenbaum ◽  
Pritam Sinharoy ◽  
Derek S. Damron ◽  
Lutz Birnbaumer ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Oxidation Products ◽  
Site Directed Mutagenesis ◽  
Trpc Channels ◽  
Lipid Oxidation Products ◽  
Transient Receptor

Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels leading to inhibition of endothelial cell (EC) migration in vitro and delayed EC healing of arterial injuries in vivo. The precise mechanism through which lysoPC activates TRPC6 channels is not known, but calmodulin (CaM) contributes to the regulation of TRPC channels. Using site-directed mutagenesis, cDNAs were generated in which Tyr99 or Tyr138 of CaM was replaced with Phe, generating mutant CaM, Phe99-CaM, or Phe138-CaM, respectively. In ECs transiently transfected with pcDNA3.1-myc-His-Phe99-CaM, but not in ECs transfected with pcDNA3.1-myc-His-Phe138-CaM, the lysoPC-induced TRPC6-CaM dissociation and TRPC6 externalization was disrupted. Also, the lysoPC-induced increase in intracellular calcium concentration was inhibited in ECs transiently transfected with pcDNA3.1-myc-His-Phe99-CaM. Blocking phosphorylation of CaM at Tyr99 also reduced CaM association with the p85 subunit and subsequent activation of phosphatidylinositol 3-kinase (PI3K). This prevented the increase in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the translocation of TRPC6 to the cell membrane and reduced the inhibition of EC migration by lysoPC. These findings suggest that lysoPC induces CaM phosphorylation at Tyr99 by a Src family kinase and that phosphorylated CaM activates PI3K to produce PIP3, which promotes TRPC6 translocation to the cell membrane.

scholarly journals TRPC5-CaV3 complex mediates Leptin-induced excitability in hypothalamic neurons

2020 ◽  
Author(s):  
Paula P. Perissinotti ◽  
Elizabeth Martínez-Hernández ◽  
Erika S. Piedras-Rentería
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Receptor Potential ◽  
Membrane Depolarization ◽  
Macromolecular Complex ◽  
Trpc Channels ◽  
Neuron Excitability ◽  
Intracellular Ca ◽  
Transient Receptor

ABSTRACTLeptin regulates hypothalamic POMC+ (pro-opiomelanocortin) neurons by inducing TRPC (Transient Receptor Potential Cation) channel-mediate membrane depolarization. Here we assessed the role of T-type channels on POMC neuron excitability and leptin-induced depolarization in vitro. We demonstrate T-type currents are indispensable for both processes, as treatment with NNC-55-0396 prevented the membrane depolarization and rheobase changes induced by leptin in cultured mouse POMC neurons. Furthermore, we demonstrate TRPC1/C5 channels and CaV3.1 and CaV3.2 channels co-exist in complex. The functional relevance of this complex was corroborated using intracellular Ca2+ chelators; intracellular BAPTA (but not EGTA) application was sufficient to preclude POMC neuron excitability by preventing leptin-induced calcium influx through TRPC channels and T-type channel function.We conclude T-type channels are integral in POMC neuron excitability. Leptin activation of TRPC channels existing in a macromolecular complex with T-type channels recruits the latter by locally-induced membrane depolarization, further depolarizing POMC neurons, triggering action potentials and excitability.

scholarly journals Linalool odor‐induced analgesia is triggered by TRPA1-independent pathway in mice

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Hideki Kashiwadani ◽  
Yurina Higa ◽  
Mitsutaka Sugimura ◽  
Tomoyuki Kuwaki
Keyword(s):  
Pain Threshold ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Analgesic Effects ◽  
Neuronal Mechanisms ◽  
Odor Exposure ◽  
Noxious Mechanical Stimulation ◽  
Transient Receptor ◽  
Deficient Mice

AbstractWe had recently reported that linalool odor exposure induced significant analgesic effects in mice and that the effects were disappeared in olfactory-deprived mice in which the olfactory epithelium was damaged, thus indicating that the effects were triggered by chemical senses evoked by linalool odor exposure. However, the peripheral neuronal mechanisms, including linalool receptors that contribute toward triggering the linalool odor-induced analgesia, still remain unexplored. In vitro studies have shown that the transient receptor potential ankyrin 1 (TRPA1) responded to linalool, thus raising the possibility that TRPA1 expressed on the trigeminal nerve terminal detects linalool odor inhaled into the nostril and triggers the analgesic effects. To address this hypothesis, we measured the behavioral pain threshold for noxious mechanical stimulation in TRPA1-deficient mice. In contrast to our expectation, we found a significant increase in the threshold after linalool odor exposure in TRPA1-deficient mice, indicating the analgesic effects of linalool odor even in TRPA1-deficient mice. Furthermore, intranasal application of TRPA1 selective antagonist did not alter the analgesic effect of linalool odor. These results showed that the linalool odor-induced analgesia was triggered by a TRPA1-independent pathway in mice.

scholarly journals The transient receptor potential, TRP4, cation channel is a novel member of the family of calmodulin binding proteins

2001 ◽  
Vol 355 (3) ◽  
pp. 663-670 ◽  
Author(s):  
Claudia TROST ◽  
Christiane BERGS ◽  
Nina HIMMERKUS ◽  
Veit FLOCKERZI
Keyword(s):  
Amino Acid ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Direct Interaction ◽  
Receptor Potential ◽  
Amino Acid Residues ◽  
Glutathione S Transferase ◽  
Calmodulin Binding ◽  
Transient Receptor

The mammalian gene products, transient receptor potential (trp)1 to trp7, are related to the Drosophila TRP and TRP-like ion channels, and are candidate proteins underlying agonist-activated Ca2+-permeable ion channels. Recently, the TRP4 protein has been shown to be part of native store-operated Ca2+-permeable channels. These channels, most likely, are composed of other proteins in addition to TRP4. In the present paper we report the direct interaction of TRP4 and calmodulin (CaM) by: (1) retention of in vitro translated TRP4 and of TRP4 protein solubilized from bovine adrenal cortex by CaM–Sepharose in the presence of Ca2+, and (2) TRP4–glutathione S-transferase pull-down experiments. Two domains of TRP4, amino acid residues 688–759 and 786–848, were identified as being able to interact with CaM. The binding of CaM to both domains occurred only in the presence of Ca2+ concentrations above 10µM, with half maximal binding occurring at 16.6µM (domain 1) and 27.9µM Ca2+ (domain 2). Synthetic peptides, encompassing the two putative CaM binding sites within these domains and covering amino acid residues 694–728 and 829–853, interacted directly with dansyl–CaM with apparent Kd values of 94–189nM. These results indicate that TRP4/Ca2+-CaM are parts of a signalling complex involved in agonist-induced Ca2+ entry.

scholarly journals Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performance

2014 ◽  
Vol 306 (4) ◽  
pp. H574-H584 ◽  
Author(s):  
Jack Rubinstein ◽  
Valerie M. Lasko ◽  
Sheryl E. Koch ◽  
Vivek P. Singh ◽  
Vinicius Carreira ◽  
...  
Keyword(s):  
Vascular Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Wild Type ◽  
Transient Receptor ◽  
Systolic And Diastolic Function ◽  
Myocyte Contractility

Transient receptor potential cation channels have been implicated in the regulation of cardiovascular function, but only recently has our laboratory described the vanilloid-2 subtype (TRPV2) in the cardiomyocyte, though its exact mechanism of action has not yet been established. This study tests the hypothesis that TRPV2 plays an important role in regulating myocyte contractility under physiological conditions. Therefore, we measured cardiac and vascular function in wild-type and TRPV2−/− mice in vitro and in vivo and found that TRPV2 deletion resulted in a decrease in basal systolic and diastolic function without affecting loading conditions or vascular tone. TRPV2 stimulation with probenecid, a relatively selective TRPV2 agonist, caused an increase in both inotropy and lusitropy in wild-type mice that was blunted in TRPV2−/− mice. We examined the mechanism of TRPV2 inotropy/lusitropy in isolated myocytes and found that it modulates Ca2+ transients and sarcoplasmic reticulum Ca2+ loading. We show that the activity of this channel is necessary for normal cardiac function and that there is increased contractility in response to agonism of TRPV2 with probenecid.

scholarly journals The Na+/Ca2+ Exchanger Inhibitor, KB-R7943, Blocks a Nonselective Cation Channel Implicated in Chemosensory Transduction

2009 ◽  
Vol 101 (3) ◽  
pp. 1151-1159 ◽  
Author(s):  
A. Pezier ◽  
Y. V. Bobkov ◽  
B. W. Ache
Keyword(s):  
Transient Receptor Potential ◽  
Single Channel ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Dependent Manner ◽  
Open Probability ◽  
Olfactory Transduction ◽  
Voltage Dependent ◽  
Chemosensory Transduction ◽  
Transient Receptor

The mechanism(s) of olfactory transduction in invertebrates remains to be fully understood. In lobster olfactory receptor neurons (ORNs), a nonselective sodium-gated cation (SGC) channel, a presumptive transient receptor potential (TRP)C channel homolog, plays a crucial role in olfactory transduction, at least in part by amplifying the primary transduction current. To better determine the functional role of the channel, it is important to selectively block the channel independently of other elements of the transduction cascade, causing us to search for specific pharmacological blockers of the SGC channel. Given evidence that the Na+/Ca2+ exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we studied this probe as a potential blocker of the lobster SGC channel. KB-R7943 reversibly blocked the SGC current in both inside- and outside-out patch recordings in a dose- and voltage-dependent manner. KB-R7943 decreased the channel open probability without changing single channel amplitude. KB-R7943 also reversibly and in a dose-dependent manner inhibited both the odorant-evoked discharge of lobster ORNs and the odorant-evoked whole cell current. Our findings strongly imply that KB-R7943 potently blocks the lobster SGC channel and likely does so directly and not through its ability to block the Na+/Ca2+ exchanger.

scholarly journals Presence of TRPA1 Modifies CD4+/CD8+ T Lymphocyte Ratio and Activation

2022 ◽  
Vol 15 (1) ◽  
pp. 57
Author(s):  
Katalin Szabó ◽  
Ágnes Kemény ◽  
Noémi Balázs ◽  
Esam Khanfar ◽  
Zoltán Sándor ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Lymphocyte Function ◽  
Targeted Deletion ◽  
Flow Cytometric ◽  
Cd8 T Lymphocyte ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Transient Receptor

Transient Receptor Potential Ankyrin 1 (TRPA1) has been reported to influence neuroinflammation and lymphocyte function. We analysed the immune phenotype and activation characteristics of TRPA1-deficient mice (knockout—KO) generated by targeted deletion of the pore-loop domain of the ion channel. We compared TRPA1 mRNA and protein expression in monocyte and lymphocyte subpopulations isolated from primary and secondary lymphatic organs of wild type (WT) and KO mice. qRT-PCR and flow cytometric studies indicated a higher level of TRPA1 in monocytes than in lymphocytes, but both were orders of magnitude lower than in sensory neurons. We found lower CD4+/CD8+ thymocyte ratios, diminished CD4/CD8 rates, and B cell numbers in the KO mice. Early activation marker CD69 was lower in CD4+ T cells of KO, while the level of CD8+/CD25+ cells was higher. In vitro TcR-mediated activation did not result in significant differences in CD69 level between WT and KO splenocytes, but lower cytokine (IL-1β, IL-6, TNF-α, IL-17A, IL-22, and RANTES) secretion was observed in KO splenocytes. Basal intracellular Ca2+ level and TcR-induced Ca2+ signal in T lymphocytes did not differ significantly, but interestingly, imiquimod-induced Ca2+ level in KO thymocytes was higher. Our results support the role of TRPA1 in the regulation of activation, cytokine production, and T and B lymphocytes composition in mice.

Regulation of Transient Receptor Potential Canonical 4 Activity by Phospholipase C-δ1

2020 ◽  
Author(s):  
Juyeon Ko ◽  
Jongyun Myeong ◽  
Misun Kwak ◽  
Insuk So
Keyword(s):  
Phospholipase C ◽  
Transient Receptor Potential ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Receptor Potential ◽  
Regulation Mechanism ◽  
Trpc Channels ◽  
Transient Receptor Potential Canonical ◽  
Cell Current ◽  
Transient Receptor

Abstract Transient receptor potential canonical (TRPC) channels are non-selective calcium-permeable cation channels. It is suggested that TRPC4β and TRPC5 channels are regulated by phospholipase C (PLC) signaling, and are especially maintained by phosphatidylinositol 4,5-bisphosphate (PIP2). The PLCδ subtype is the most Ca2+-sensitive form among the isozymes which cleaves phospholipids to respond to the calcium rise. In this study, we investigated the regulation mechanism of TRPC channel by Ca2+, PLCδ1 and PIP2 signaling cascades. The interaction between TRPC4β and PLCδ1 was identified through the Fӧster resonance energy transfer (FRET) and co-immunoprecipitation (Co-IP). With the electrophysiological experiments, we found that TRPC4β-bound PLCδ1 reduces the overall whole-cell current of channel. The Ca2+-via opened channel promotes the activation of PLCδ1, which subsequently decreases PIP2 level. By comparison TRPC4β activity with or without PLCδ1 using differently [Ca2+]i buffered solution, we demonstrated that PLCδ1 functions in normal condition with physiological calcium range. The negative regulation effect of PLCδ1 on TRPC4β helps to elucidate the roles of each PIP2 binding residues whether they are concerned in channel maintenance or inhibition of channel activity.

scholarly journals Canonical Transient Receptor Potential (TRPC) Channels in Nociception and Pathological Pain

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Zhi-Chuan Sun ◽  
Sui-Bin Ma ◽  
Wen-Guang Chu ◽  
Dong Jia ◽  
Ceng Luo
Keyword(s):  
Chronic Pain ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Canonical Transient Receptor Potential ◽  
Abnormal Increase ◽  
Pathological Pain ◽  
Transient Receptor ◽  
Underlying Mechanisms

Chronic pathological pain is one of the most intractable clinical problems faced by clinicians and can be devastating for patients. Despite much progress we have made in understanding chronic pain in the last decades, its underlying mechanisms remain elusive. It is assumed that abnormal increase of calcium levels in the cells is a key determinant in the transition from acute to chronic pain. Exploring molecular players mediating Ca2+ entry into cells and molecular mechanisms underlying activity-dependent changes in Ca2+ signaling in the somatosensory pain pathway is therefore helpful towards understanding the development of chronic, pathological pain. Canonical transient receptor potential (TRPC) channels form a subfamily of nonselective cation channels, which permit the permeability of Ca2+ and Na+ into the cells. Initiation of Ca2+ entry pathways by these channels triggers the development of many physiological and pathological functions. In this review, we will focus on the functional implication of TRPC channels in nociception with the elucidation of their role in the detection of external stimuli and nociceptive hypersensitivity.

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