scholarly journals TRPC Channels in Cardiac Plasticity

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 454 ◽  
Author(s):  
Takuro Numaga-Tomita ◽  
Motohiro Nishida
Keyword(s):  
Cardiac Remodeling ◽  
Structural Changes ◽  
Cancer Cachexia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Trpc Channels ◽  
Transient Receptor ◽  
Species Production ◽  
Near Future

The heart flexibly changes its structure in response to changing environments and oxygen/nutrition demands of the body. Increased and decreased mechanical loading induces hypertrophy and atrophy of cardiomyocytes, respectively. In physiological conditions, these structural changes of the heart are reversible. However, chronic stresses such as hypertension or cancer cachexia cause irreversible remodeling of the heart, leading to heart failure. Accumulating evidence indicates that calcium dyshomeostasis and aberrant reactive oxygen species production cause pathological heart remodeling. Canonical transient receptor potential (TRPC) is a nonselective cation channel subfamily whose multimodal activation or modulation of channel activity play important roles in a plethora of cellular physiology. Roles of TRPC channels in cardiac physiology have been reported in pathological cardiac remodeling. In this review, we summarize recent findings regarding the importance of TRPC channels in flexible cardiac remodeling (i.e., cardiac plasticity) in response to environmental stresses and discuss questions that should be addressed in the near future.

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 Functional Interaction among KCa and TRP Channels for Cardiovascular Physiology: Modern Perspectives on Aging and Chronic Disease

2019 ◽  
Vol 20 (6) ◽  
pp. 1380 ◽  
Author(s):  
Erik Behringer ◽  
Md Hakim
Keyword(s):  
Blood Flow ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
The Body ◽  
Cardiovascular Physiology ◽  
Treatment And Prevention ◽  
Kca Channels ◽  
Age Related ◽  
Transient Receptor

Effective delivery of oxygen and essential nutrients to vital organs and tissues throughout the body requires adequate blood flow supplied through resistance vessels. The intimate relationship between intracellular calcium ([Ca2+]i) and regulation of membrane potential (Vm) is indispensable for maintaining blood flow regulation. In particular, Ca2+-activated K+ (KCa) channels were ascertained as transducers of elevated [Ca2+]i signals into hyperpolarization of Vm as a pathway for decreasing vascular resistance, thereby enhancing blood flow. Recent evidence also supports the reverse role for KCa channels, in which they facilitate Ca2+ influx into the cell interior through open non-selective cation (e.g., transient receptor potential; TRP) channels in accord with robust electrical (hyperpolarization) and concentration (~20,000-fold) transmembrane gradients for Ca2+. Such an arrangement supports a feed-forward activation of Vm hyperpolarization while potentially boosting production of nitric oxide. Furthermore, in vascular types expressing TRP channels but deficient in functional KCa channels (e.g., collecting lymphatic endothelium), there are profound alterations such as downstream depolarizing ionic fluxes and the absence of dynamic hyperpolarizing events. Altogether, this review is a refined set of evidence-based perspectives focused on the role of the endothelial KCa and TRP channels throughout multiple experimental animal models and vascular types. We discuss the diverse interactions among KCa and TRP channels to integrate Ca2+, oxidative, and electrical signaling in the context of cardiovascular physiology and pathology. Building from a foundation of cellular biophysical data throughout a wide and diverse compilation of significant discoveries, a translational narrative is provided for readers toward the treatment and prevention of chronic, age-related cardiovascular disease.

scholarly journals TRP Channels as Sensors of Aldehyde and Oxidative Stress

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1401
Author(s):  
Katharina E. M. Hellenthal ◽  
Laura Brabenec ◽  
Eric R. Gross ◽  
Nana-Maria Wagner
Keyword(s):  
Lipid Peroxidation ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Treatment Options ◽  
Receptor Potential ◽  
The Body ◽  
Trp Channel ◽  
Alcoholic Beverages ◽  
Organ Injury ◽  
Transient Receptor

The transient receptor potential (TRP) cation channel superfamily comprises more than 50 channels that play crucial roles in physiological processes. TRP channels are responsive to several exogenous and endogenous biomolecules, with aldehydes emerging as a TRP channel trigger contributing to a cellular cascade that can lead to disease pathophysiology. The body is not only exposed to exogenous aldehydes via tobacco products or alcoholic beverages, but also to endogenous aldehydes triggered by lipid peroxidation. In response to lipid peroxidation from inflammation or organ injury, polyunsaturated fatty acids undergo lipid peroxidation to aldehydes, such as 4-hydroxynonenal. Reactive aldehydes activate TRP channels via aldehyde-induced protein adducts, leading to the release of pro-inflammatory mediators driving the pathophysiology caused by cellular injury, including inflammatory pain and organ reperfusion injury. Recent studies have outlined how aldehyde dehydrogenase 2 protects against aldehyde toxicity through the clearance of toxic aldehydes, indicating that targeting the endogenous aldehyde metabolism may represent a novel treatment strategy. An addition approach can involve targeting specific TRP channel regions to limit the triggering of a cellular cascade induced by aldehydes. In this review, we provide a comprehensive summary of aldehydes, TRP channels, and their interactions, as well as their role in pathological conditions and the different therapeutical treatment options.

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.

scholarly journals Structure–Function Relationship and Physiological Roles of Transient Receptor Potential Canonical (TRPC) 4 and 5 Channels

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 73
Author(s):  
Jinsung Kim ◽  
Juyeon Ko ◽  
Chansik Hong ◽  
Insuk So
Keyword(s):  
Ion Channels ◽  
Structure Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Transient Receptor Potential Canonical ◽  
Structure Function Relationship ◽  
Transient Receptor ◽  
Function Relationship ◽  
Relationship Of

The study of the structure–function relationship of ion channels has been one of the most challenging goals in contemporary physiology. Revelation of the three-dimensional (3D) structure of ion channels has facilitated our understanding of many of the submolecular mechanisms inside ion channels, such as selective permeability, voltage dependency, agonist binding, and inter-subunit multimerization. Identifying the structure–function relationship of the ion channels is clinically important as well since only such knowledge can imbue potential therapeutics with practical possibilities. In a sense, recent advances in the understanding of the structure–relationship of transient receptor potential canonical (TRPC) channels look promising since human TRPC channels are calcium-permeable, non-selective cation channels expressed in many tissues such as the gastrointestinal (GI) tract, kidney, heart, vasculature, and brain. TRPC channels are known to regulate GI contractility and motility, pulmonary hypertension, right ventricular hypertrophy, podocyte injury, seizure, fear, anxiety-like behavior, and many others. In this article, we tried to elaborate recent findings of Cryo-EM (cryogenic-electron microscopy) based structural information of TRPC 4 and 5 channels and domain-specific functions of the channel, such as G-protein mediated activation mechanism, extracellular modification of the channel, homo/hetero-tetramerization, and pharmacological gating mechanisms.

scholarly journals The Basal Pharmacology of Palmitoylethanolamide

2020 ◽  
Vol 21 (21) ◽  
pp. 7942 ◽  
Author(s):  
Linda Rankin ◽  
Christopher J. Fowler
Keyword(s):  
Transient Receptor Potential ◽  
Biological Effects ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmacokinetic Properties ◽  
Endogenous Compound ◽  
Transient Receptor

Palmitoylethanolamide (PEA, N-hexadecanoylethanolamide) is an endogenous compound belonging to the family of N-acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.

scholarly journals TRPC expression in mesenchymal stem cells

2010 ◽  
Vol 15 (4) ◽  
Author(s):  
Frederic Torossian ◽  
Aurelie Bisson ◽  
Jean-Pierre Vannier ◽  
Olivier Boyer ◽  
Marek Lamacz
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cell Biology ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Stem Cell Proliferation ◽  
Regulatory Processes ◽  
Transient Receptor

AbstractTransient receptor potential canonical (TRPC) channels are key players in calcium homeostasis and various regulatory processes in cell biology. Little is currently known about the TRPC subfamily members in mesenchymal stem cells (MSC), where they could play a role in cell proliferation. We report on the presence of TRPC1, 2, 4 and 6 mRNAs in MSC. Western blot and immunofluorescence staining indicate a membrane and intracellular distribution of TRPC1. Furthermore, the decrease in the level of TRPC1 protein caused by RNA interference is accompanied by the downregulation of cell proliferation. These results indicate that MSC express TRPC1, 2, 4 and 6 mRNA and that TRPC1 may play a role in stem cell proliferation.

scholarly journals Light-Mediated Control over TRPC3-Mediated NFAT Signaling

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 556 ◽  
Author(s):  
Annarita Graziani ◽  
Bernadett Bacsa ◽  
Denis Krivic ◽  
Patrick Wiedner ◽  
Sanja Curcic ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Nuclear Translocation ◽  
Receptor Potential ◽  
Hek293 Cells ◽  
Trpc Channels ◽  
Activated T Cells ◽  
Precise Control ◽  
All Optical ◽  
Tight Linkage ◽  
Transient Receptor

Canonical transient receptor potential (TRPC) channels were identified as key players in maladaptive remodeling, with nuclear factor of activated T-cells (NFAT) transcription factors serving as downstream targets of TRPC-triggered Ca2+ entry in these pathological processes. Strikingly, the reconstitution of TRPC-NFAT signaling by heterologous expression yielded controversial results. Specifically, nuclear translocation of NFAT1 was found barely responsive to recombinant TRPC3, presumably based on the requirement of certain spatiotemporal signaling features. Here, we report efficient control of NFAT1 nuclear translocation in human embryonic kidney 293 (HEK293) cells by light, using a new photochromic TRPC benzimidazole activator (OptoBI-1) and a TRPC3 mutant with modified activator sensitivity. NFAT1 nuclear translocation was measured along with an all-optical protocol to record local and global Ca2+ pattern generated during light-mediated activation/deactivation cycling of TRPC3. Our results unveil the ability of wild-type TRPC3 to produce constitutive NFAT nuclear translocation. Moreover, we demonstrate that TRPC3 mutant that lacks basal activity enables spatiotemporally precise control over NFAT1 activity by photopharmacology. Our results suggest tight linkage between TRPC3 activity and NFAT1 nuclear translocation based on global cellular Ca2+ signals.

scholarly journals Effect of Lipoxin A4on Lipopolysaccharide-Induced Endothelial Hyperpermeability

2011 ◽  
Vol 11 ◽  
pp. 1056-1067 ◽  
Author(s):  
Huayan Pang ◽  
Pan Yi ◽  
Ping Wu ◽  
Zhuoya Liu ◽  
Zhongjie Liu ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Umbilical Vein ◽  
Receptor Potential ◽  
Related Factor ◽  
Lipoxin A4 ◽  
Cellular Calcium ◽  
Normal Expression ◽  
Transient Receptor ◽  
Umbilical Vein Endothelial Cells ◽  
Species Production

Excessive oxidative stress, decreased antioxidant capacity, and enhanced cellular calcium levels are initial factors that cause endothelial cell (EC) hyperpermeability, which represents a crucial event in the pathogenesis of pre-eclampsia. Lipoxin A4 (LXA4) strongly attenuated lipopolysaccharide (LPS)-induced hyperpermeability through maintaining the normal expression of VE-cadherin and β-catenin. This effect was mainly mediated by a specific LXA4receptor. LXA4could also obviously inhibit LPS-induced elevation of the cellular calcium level and up-regulation of the transient receptor potential protein family C 1, an important calcium channel in ECs. At the same time, LXA4strongly blocked LPS-triggered reactive oxidative species production, while it promoted the expression of the NF-E2 related factor 2 (Nrf2) protein. Our findings demonstrate that LXA4could prevent the EC hyperpermeability induced by LPS in human umbilical vein endothelial cells (HUVECs), under which the possible mechanism is through Nrf2 as well as Ca2+-sensitive pathways.

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