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TRP Channels in Health and Disease
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TRP Channels in Health and Disease

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 December 2018) | Viewed by 91393

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Alexander Dietrich

E-Mail Website
Guest Editor
Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universitat Muenchen, Munich, Germany
Interests: TRP channels; lung physiology and pathophysiology; TRP-deficient mouse models; TRP modulators as therapeutic options

Special Issue Information

Dear Colleagues,

Transient receptor potential (TRP) channels represent an extended family of 28 members fulfilling multiple roles in the living organism. Over the last few years, new findings on TRP channels reveal an exceptionally broad spectrum as cellular sensors and effectors. Body temperature control, transmitter release from neurons, mineral homeostasis, chemical sensing, and survival mechanisms in a challenging environment are only a few functions which are tightly controlled by these channels. More than 20 hereditary human diseases in areas as diverse as neurology, cardiology, pulmonology, nephrology, dermatology, and urology caused by mutations in 11 TRP genes emphasize their truly remarkable diversity and underscore their essential role in vivo. Moreover, TRP channels are important pharmacological targets for specific novel therapeutic treatment options for patients suffering from diseases caused by dysfunctional TRP proteins. Along these lines, specific TRP inhibitors and activators were identified in the lasts years and are now tested in vitro and in vivo. At the cellular level, TRP channels can be activated by diverse chemical and physical stimuli and are involved in the regulation of the influx of external Ca2+—a universal second messenger regulating diverse cellular functions. However, TRP proteins do not function in isolation, but are organized as structural and functional protein modules in complex signal transduction pathways to execute essential tasks of the cell which are still under investigation. This special issue of Cells will feature a collection of excellent review articles summarizing the current state of the art on TRP channel research with a main focus on TRP channel activation, their physiological and pathophysiological function, and their roles as pharmacological targets for future therapeutic options.

Prof. Dr. Alexander Dietrich
Guest Editor

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Keywords

  • TRP channels
  • TRP function on an organismal, cellular, and molecular level
  • TRPs and pathophysiological function
  • TRP modulators as new therapeutic options

Published Papers (16 papers)

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Editorial

Jump to: Research, Review

5 pages, 445 KiB  
Editorial
Transient Receptor Potential (TRP) Channels in Health and Disease
by Alexander Dietrich
Cells 2019, 8(5), 413; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8050413 - 04 May 2019
Cited by 28 | Viewed by 5095
Abstract
Almost 25 years ago, the first mammalian transient receptor potential (TRP) channel, now named TRPC1, was cloned and published (reviewed in [...] Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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Research

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16 pages, 3619 KiB  
Article
Bioavailable Menthol (Transient Receptor Potential Melastatin-8 Agonist) Induces Energy Expending Phenotype in Differentiating Adipocytes
by Pragyanshu Khare, Aakriti Chauhan, Vibhu Kumar, Jasleen Kaur, Neha Mahajan, Vijay Kumar, Adam Gesing, Kanwaljit Chopra, Kanthi Kiran Kondepudi and Mahendra Bishnoi
Cells 2019, 8(5), 383; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8050383 - 26 Apr 2019
Cited by 20 | Viewed by 5544
Abstract
Recent evidence supports the role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in a TRPM8 dependent and independent manner. The present study was designed to analyse whether oral and topical administration of menthol [...] Read more.
Recent evidence supports the role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in a TRPM8 dependent and independent manner. The present study was designed to analyse whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to directlyinduce desired energy expenditure effects. GC-FID was performed to study menthol bioavailability in serum and subcutaneous white adipose tissue following oral and topical administration. Further, 3T3L1 adipocytes were treated with bioavailable menthol doses and different parameters (lipid accumulation, “browning/brite” and energy expenditure gene expression, metal analysis, mitochondrial complex’s gene expression) were studied. No difference was observed in serum levels but significant difference was seen in the menthol concentration on subcutaneous adipose tissues after oral and topical application. Menthol administration at bioavailable doses significantly increased “browning/brite” and energy expenditure phenotype, enhanced mitochondrial activity related gene expression, increased metal concentration during adipogenesis but did not alter the lipid accumulation as well as acute experiments were performed with lower dose of menthol on mature adipocytes In conclusion, the present study provides evidence that bioavailable menthol after single oral and topical administration is sufficient to induce “brite” phenotype in subcutaneous adipose tissue However, critical dose characterization for its clinical utility is required. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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20 pages, 5090 KiB  
Article
Purification of Functional Human TRP Channels Recombinantly Produced in Yeast
by Liying Zhang, Kaituo Wang, Dan Arne Klaerke, Kirstine Calloe, Lillian Lowrey, Per Amstrup Pedersen, Pontus Gourdon and Kamil Gotfryd
Cells 2019, 8(2), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8020148 - 11 Feb 2019
Cited by 4 | Viewed by 6288
Abstract
(1) Background: Human transient receptor potential (TRP) channels constitute a large family of ion-conducting membrane proteins that allow the sensation of environmental cues. As the dysfunction of TRP channels contributes to the pathogenesis of many widespread diseases, including cardiac disorders, these proteins also [...] Read more.
(1) Background: Human transient receptor potential (TRP) channels constitute a large family of ion-conducting membrane proteins that allow the sensation of environmental cues. As the dysfunction of TRP channels contributes to the pathogenesis of many widespread diseases, including cardiac disorders, these proteins also represent important pharmacological targets. TRP channels are typically produced using expensive and laborious mammalian or insect cell-based systems. (2) Methods: We demonstrate an alternative platform exploiting the yeast Saccharomyces cerevisiae capable of delivering high yields of functional human TRP channels. We produce 11 full-length human TRP members originating from four different subfamilies, purify a selected subset of these to a high homogeneity and confirm retained functionality using TRPM8 as a model target. (3) Results: Our findings demonstrate the potential of the described production system for future functional, structural and pharmacological studies of human TRP channels. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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14 pages, 2102 KiB  
Article
Manganese Suppresses the Haploinsufficiency of Heterozygous trpy1Δ/TRPY1 Saccharomyces cerevisiae Cells and Stimulates the TRPY1-Dependent Release of Vacuolar Ca2+ under H2O2 Stress
by Lavinia L. Ruta, Ioana Nicolau, Claudia V. Popa and Ileana C. Farcasanu
Cells 2019, 8(2), 79; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8020079 - 22 Jan 2019
Cited by 4 | Viewed by 2931
Abstract
Transient potential receptor (TRP) channels are conserved cation channels found in most eukaryotes, known to sense a variety of chemical, thermal or mechanical stimuli. The Saccharomyces cerevisiae TRPY1 is a TRP channel with vacuolar localization involved in the cellular response to hyperosmotic shock [...] Read more.
Transient potential receptor (TRP) channels are conserved cation channels found in most eukaryotes, known to sense a variety of chemical, thermal or mechanical stimuli. The Saccharomyces cerevisiae TRPY1 is a TRP channel with vacuolar localization involved in the cellular response to hyperosmotic shock and oxidative stress. In this study, we found that S. cerevisiae diploid cells with heterozygous deletion in TRPY1 gene are haploinsufficient when grown in synthetic media deficient in essential metal ions and that this growth defect is alleviated by non-toxic Mn2+ surplus. Using cells expressing the Ca2+-sensitive photoprotein aequorin we found that Mn2+ augmented the Ca2+ flux into the cytosol under oxidative stress, but not under hyperosmotic shock, a trait that was absent in the diploid cells with homozygous deletion of TRPY1 gene. TRPY1 activation under oxidative stress was diminished in cells devoid of Smf1 (the Mn2+-high-affinity plasma membrane transporter) but it was clearly augmented in cells lacking Pmr1 (the endoplasmic reticulum (ER)/Golgi located ATPase responsible for Mn2+ detoxification via excretory pathway). Taken together, these observations lead to the conclusion that increased levels of intracytosolic Mn2+ activate TRPY1 in the response to oxidative stress. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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17 pages, 1786 KiB  
Article
Transient Receptor Potential Channel A1 (TRPA1) Regulates Sulfur Mustard-Induced Expression of Heat Shock 70 kDa Protein 6 (HSPA6) In Vitro
by Robin Lüling, Harald John, Thomas Gudermann, Horst Thiermann, Harald Mückter, Tanja Popp and Dirk Steinritz
Cells 2018, 7(9), 126; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7090126 - 31 Aug 2018
Cited by 10 | Viewed by 4532
Abstract
The chemosensory transient receptor potential ankyrin 1 (TRPA1) ion channel perceives different sensory stimuli. It also interacts with reactive exogenous compounds including the chemical warfare agent sulfur mustard (SM). Activation of TRPA1 by SM results in elevation of intracellular calcium levels but the [...] Read more.
The chemosensory transient receptor potential ankyrin 1 (TRPA1) ion channel perceives different sensory stimuli. It also interacts with reactive exogenous compounds including the chemical warfare agent sulfur mustard (SM). Activation of TRPA1 by SM results in elevation of intracellular calcium levels but the cellular consequences are not understood so far. In the present study we analyzed SM-induced and TRPA1-mediated effects in human TRPA1-overexpressing HEK cells (HEKA1) and human lung epithelial cells (A549) that endogenously exhibit TRPA1. The specific TRPA1 inhibitor AP18 was used to distinguish between SM-induced and TRPA1-mediated or TRPA1-independent effects. Cells were exposed to 600 µM SM and proteome changes were investigated 24 h afterwards by 2D gel electrophoresis. Protein spots with differential staining levels were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nano liquid chromatography electrospray ionization tandem mass spectrometry. Results were verified by RT-qPCR experiments in both HEKA1 or A549 cells. Heat shock 70 kDa protein 6 (HSPA6) was identified as an SM-induced and TRPA1-mediated protein. AP18 pre-treatment diminished the up-regulation. RT-qPCR measurements verified these results and further revealed a time-dependent regulation. Our results demonstrate that SM-mediated activation of TRPA1 influences the protein expression and confirm the important role of TRPA1 ion channels in the molecular toxicology of SM. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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14 pages, 2625 KiB  
Article
GABAB Receptors Augment TRPC3-Mediated Slow Excitatory Postsynaptic Current to Regulate Cerebellar Purkinje Neuron Response to Type-1 Metabotropic Glutamate Receptor Activation
by Jinbin Tian and Michael X. Zhu
Cells 2018, 7(8), 90; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7080090 - 29 Jul 2018
Cited by 8 | Viewed by 5117
Abstract
During strong parallel fiber stimulation, glutamate released at parallel fiber-Purkinje cell synapses activates type-1 metabotropic glutamate receptor (mGluR1) to trigger a slow excitatory postsynaptic current (sEPSC) in cerebellar Purkinje neurons. The sEPSC is mediated by transient receptor potential canonical 3 (TRPC3) channels. Often [...] Read more.
During strong parallel fiber stimulation, glutamate released at parallel fiber-Purkinje cell synapses activates type-1 metabotropic glutamate receptor (mGluR1) to trigger a slow excitatory postsynaptic current (sEPSC) in cerebellar Purkinje neurons. The sEPSC is mediated by transient receptor potential canonical 3 (TRPC3) channels. Often co-localized with mGluR1 in Purkinje neuron dendrites are type B γ-aminobutyric acid receptors (GABABRs) that respond to inhibitory synaptic inputs from interneurons located in the molecular layer of cerebellar cortex. It has been shown that activation of postsynaptic GABABRs potentiates mGluR1 activation-evoked sEPSC in Purkinje cells, but the underlying molecular mechanism remains elusive. Here we report that the augmentation of mGluR1-sEPSC by GABABR activation in Purkinje neurons is completely absent in TRPC3 knockout mice, but totally intact in TRPC1-, TRPC4-, and TRPC1,4,5,6-knockout mice, suggesting that TRPC3 is the only TRPC isoform that mediates the potentiation. Moreover, our results indicate that the potentiation reflects a postsynaptic mechanism that requires both GABABRs and mGluR1 because it is unaffected by blocking neurotransmission with tetrodotoxin but blocked by inhibiting either GABABRs or mGluR1. Furthermore, we show that the co-stimulation of GABABRs has an effect on shaping the response of Purkinje cell firing to mGluR1-sEPSC, revealing a new function of inhibitory input on excitatory neurotransmission. We conclude that postsynaptic GABABRs regulate Purkinje cell responses to strong glutamatergic stimulation through modulation of mGluR1-TRPC3 coupling. Since mGluR1-TRPC3 coupling is essential in cerebellar long-term depression, synapse elimination, and motor coordination, our findings may have implications in essential cerebellar functions, such as motor coordination and learning. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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19 pages, 9071 KiB  
Article
TRPV1-Like Immunoreactivity in the Human Locus K, a Distinct Subregion of the Cuneate Nucleus
by Marina Del Fiacco, Maria Pina Serra, Marianna Boi, Laura Poddighe, Roberto Demontis, Antonio Carai and Marina Quartu
Cells 2018, 7(7), 72; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7070072 - 08 Jul 2018
Cited by 2 | Viewed by 3938
Abstract
The presence of transient receptor potential vanilloid type-1 receptor (TRPV1)-like immunoreactivity (LI), in the form of nerve fibres and terminals, is shown in a set of discrete gray matter subregions placed in the territory of the human cuneate nucleus. We showed previously that [...] Read more.
The presence of transient receptor potential vanilloid type-1 receptor (TRPV1)-like immunoreactivity (LI), in the form of nerve fibres and terminals, is shown in a set of discrete gray matter subregions placed in the territory of the human cuneate nucleus. We showed previously that those subregions share neurochemical and structural features with the protopathic nuclei and, after the ancient name of our town, collectively call them Locus Karalis, and briefly Locus K. TRPV1-LI in the Locus K is codistributed, though not perfectly overlapped, with that of the neuropeptides calcitonin gene-related peptide and substance P, the topography of the elements immunoreactive to the three markers, in relation to each other, reflecting that previously described in the caudal spinal trigeminal nucleus. Myelin stainings show that myelinated fibres, abundant in the cuneate, gracile and trigeminal magnocellular nuclei, are scarce in the Locus K as in the trigeminal substantia gelatinosa. Morphometric analysis shows that cell size and density of Locus K neurons are consistent with those of the trigeminal substantia gelatinosa and significantly different from those of the magnocellular trigeminal, solitary and dorsal column nuclei. We propose that Locus K is a special component of the human dorsal column nuclei. Its functional role remains to be determined, but TRPV1 appears to play a part in it. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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10 pages, 3648 KiB  
Article
Expression Profiling of the Transient Receptor Potential Vanilloid (TRPV) Channels 1, 2, 3 and 4 in Mucosal Epithelium of Human Ulcerative Colitis
by Theodoros Rizopoulos, Helen Papadaki-Petrou and Martha Assimakopoulou
Cells 2018, 7(6), 61; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7060061 - 15 Jun 2018
Cited by 36 | Viewed by 4998
Abstract
The Transient Receptor Potential (TRP) family of selective and non-selective ion channels is well represented throughout the mammalian gastrointestinal track. Several members of the Transient Receptor Potential Vanilloid (TRPV) subfamily have been identified in contributing to modulation of mobility, secretion and sensitivity of [...] Read more.
The Transient Receptor Potential (TRP) family of selective and non-selective ion channels is well represented throughout the mammalian gastrointestinal track. Several members of the Transient Receptor Potential Vanilloid (TRPV) subfamily have been identified in contributing to modulation of mobility, secretion and sensitivity of the human intestine. Previous studies have focused on the detection of TRPV mRNA levels in colon tissue of patients with inflammatory bowel disease (IBD) whereas little information exists regarding TRPV channel expression in the colonic epithelium. The aim of this study was to evaluate the expression levels of TRPV1, TRPV2, TRPV3 and TRPV4 in mucosa epithelial cells of colonic biopsies from patients with ulcerative colitis (UC) in comparison to colonic resections from non-IBD patients (control group). Immunohistochemistry, using specific antibodies and quantitative analyses of TRPV-immunostained epithelial cells, was performed in semi-serial sections of the samples. TRPV1 expression was significantly decreased whereas TRPV4 expression was significantly increased in the colonic epithelium of UC patients compared to patients in the control group (p < 0.05). No significant difference for TRPV2 and TRPV3 expression levels between UC and control specimens was detected (p > 0.05). There was no correlation between TRPV channel expression and the clinical features of the disease (p > 0.05). Further investigation is needed to clarify the role of TRPV channels in human bowel inflammatory response. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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Review

Jump to: Editorial, Research

13 pages, 578 KiB  
Review
Emerging Roles of Diacylglycerol-Sensitive TRPC4/5 Channels
by Michael Mederos y Schnitzler, Thomas Gudermann and Ursula Storch
Cells 2018, 7(11), 218; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7110218 - 20 Nov 2018
Cited by 21 | Viewed by 4802
Abstract
Transient receptor potential classical or canonical 4 (TRPC4) and TRPC5 channels are members of the classical or canonical transient receptor potential (TRPC) channel family of non-selective cation channels. TRPC4 and TRPC5 channels are widely accepted as receptor-operated cation channels that are activated in [...] Read more.
Transient receptor potential classical or canonical 4 (TRPC4) and TRPC5 channels are members of the classical or canonical transient receptor potential (TRPC) channel family of non-selective cation channels. TRPC4 and TRPC5 channels are widely accepted as receptor-operated cation channels that are activated in a phospholipase C-dependent manner, following the Gq/11 protein-coupled receptor activation. However, their precise activation mechanism has remained largely elusive for a long time, as the TRPC4 and TRPC5 channels were considered as being insensitive to the second messenger diacylglycerol (DAG) in contrast to the other TRPC channels. Recent findings indicate that the C-terminal interactions with the scaffolding proteins Na+/H+ exchanger regulatory factor 1 and 2 (NHERF1 and NHERF2) dynamically regulate the DAG sensitivity of the TRPC4 and TRPC5 channels. Interestingly, the C-terminal NHERF binding suppresses, while the dissociation of NHERF enables, the DAG sensitivity of the TRPC4 and TRPC5 channels. This leads to the assumption that all of the TRPC channels are DAG sensitive. The identification of the regulatory function of the NHERF proteins in the TRPC4/5-NHERF protein complex offers a new starting point to get deeper insights into the molecular basis of TRPC channel activation. Future studies will have to unravel the physiological and pathophysiological functions of this multi-protein channel complex. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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16 pages, 2246 KiB  
Review
The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis
by Wiebke Nadolni and Susanna Zierler
Cells 2018, 7(8), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7080109 - 17 Aug 2018
Cited by 42 | Viewed by 7362
Abstract
The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in [...] Read more.
The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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22 pages, 2666 KiB  
Review
TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity—A Structured Review
by Dirk Steinritz, Bernhard Stenger, Alexander Dietrich, Thomas Gudermann and Tanja Popp
Cells 2018, 7(8), 98; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7080098 - 07 Aug 2018
Cited by 32 | Viewed by 5529
Abstract
Chemicals can exhibit significant toxic properties. While for most compounds, unspecific cell damaging processes are assumed, a plethora of chemicals exhibit characteristic odors, suggesting a more specific interaction with the human body. During the last few years, G-protein-coupled receptors and especially chemosensory ion [...] Read more.
Chemicals can exhibit significant toxic properties. While for most compounds, unspecific cell damaging processes are assumed, a plethora of chemicals exhibit characteristic odors, suggesting a more specific interaction with the human body. During the last few years, G-protein-coupled receptors and especially chemosensory ion channels of the transient receptor potential family (TRP channels) were identified as defined targets for several chemicals. In some cases, TRP channels were suggested as being causal for toxicity. Therefore, these channels have moved into the spotlight of toxicological research. In this review, we screened available literature in PubMed that deals with the role of chemical-sensing TRP channels in specific organ systems. TRPA1, TRPM and TRPV channels were identified as essential chemosensors in the nervous system, the upper and lower airways, colon, pancreas, bladder, skin, the cardiovascular system, and the eyes. Regarding TRP channel subtypes, A1, M8, and V1 were found most frequently associated with toxicity. They are followed by V4, while other TRP channels (C1, C4, M5) are only less abundantly expressed in this context. Moreover, TRPA1, M8, V1 are co-expressed in most organs. This review summarizes organ-specific toxicological roles of TRP channels. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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13 pages, 910 KiB  
Review
TRPC3 as a Target of Novel Therapeutic Interventions
by Oleksandra Tiapko and Klaus Groschner
Cells 2018, 7(7), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7070083 - 22 Jul 2018
Cited by 38 | Viewed by 5503
Abstract
TRPC3 is one of the classical members of the mammalian transient receptor potential (TRP) superfamily of ion channels. TRPC3 is a molecule with intriguing sensory features including the direct recognition of and activation by diacylglycerols (DAG). Although TRPC3 channels are ubiquitously expressed, they [...] Read more.
TRPC3 is one of the classical members of the mammalian transient receptor potential (TRP) superfamily of ion channels. TRPC3 is a molecule with intriguing sensory features including the direct recognition of and activation by diacylglycerols (DAG). Although TRPC3 channels are ubiquitously expressed, they appear to control functions of the cardiovascular system and the brain in a highly specific manner. Moreover, a role of TRPC3 in immunity, cancer, and tissue remodeling has been proposed, generating much interest in TRPC3 as a target for pharmacological intervention. Advances in the understanding of molecular architecture and structure-function relations of TRPC3 have been the foundations for novel therapeutic approaches, such as photopharmacology and optochemical genetics of TRPC3. This review provides an account of advances in therapeutic targeting of TRPC3 channels. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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18 pages, 6838 KiB  
Review
TRP Channel Involvement in Salivary Glands—Some Good, Some Bad
by Xibao Liu, Hwei Ling Ong and Indu Ambudkar
Cells 2018, 7(7), 74; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7070074 - 11 Jul 2018
Cited by 27 | Viewed by 8452
Abstract
Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral [...] Read more.
Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Secretion of fluid by salivary glands is stimulated by activation of specific receptors on acinar cell plasma membrane and is mediated by an increase in cytosolic [Ca2+] ([Ca2+]i). The increase in [Ca2+]i regulates a number of ion channels and transporters that are required for establishing an osmotic gradient that drives water flow via aquaporin water channels in the apical membrane. The Store-Operated Ca2+ Entry (SOCE) mechanism, which is regulated in response to depletion of ER-Ca2+, determines the sustained [Ca2+]i increase required for prolonged fluid secretion. Core components of SOCE in salivary gland acinar cells are Orai1 and STIM1. In addition, TRPC1 is a major and non-redundant contributor to SOCE and fluid secretion in salivary gland acinar and ductal cells. Other TRP channels that contribute to salivary flow are TRPC3 and TRPV4, while presence of others, including TRPM8, TRPA1, TRPV1, and TRPV3, have been identified in the gland. Loss of salivary gland function leads to dry mouth conditions, or xerostomia, which is clinically seen in patients who have undergone radiation treatment for head-and-neck cancers, and those with the autoimmune exocrinopathy, Sjögren’s syndrome (pSS). TRPM2 is a unique TRP channel that acts as a sensor for intracellular ROS. We will discuss recent studies reported by us that demonstrate a key role for TRPM2 in radiation-induced salivary gland dysfunction. Further, there is increasing evidence that TRPM2 might be involved in inflammatory processes. These interesting findings point to the possible involvement of TRPM2 in Sjögren’s Syndrome, although further studies will be required to identify the exact role of TRPM2 in this disease. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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24 pages, 851 KiB  
Review
Ion Channels and Transporters in Inflammation: Special Focus on TRP Channels and TRPC6
by Giuseppe A. Ramirez, Lavinia A. Coletto, Clara Sciorati, Enrica P. Bozzolo, Paolo Manunta, Patrizia Rovere-Querini and Angelo A. Manfredi
Cells 2018, 7(7), 70; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7070070 - 04 Jul 2018
Cited by 35 | Viewed by 6601
Abstract
Allergy and autoimmune diseases are characterised by a multifactorial pathogenic background. Several genes involved in the control of innate and adaptive immunity have been associated with diseases and variably combine with each other as well as with environmental factors and epigenetic processes to [...] Read more.
Allergy and autoimmune diseases are characterised by a multifactorial pathogenic background. Several genes involved in the control of innate and adaptive immunity have been associated with diseases and variably combine with each other as well as with environmental factors and epigenetic processes to shape the characteristics of individual manifestations. Systemic or local perturbations in salt/water balance and in ion exchanges between the intra- and extracellular spaces or among tissues play a role. In this field, usually referred to as elementary immunology, novel evidence has been recently acquired on the role of members of the transient potential receptor (TRP) channel family in several cellular mechanisms of potential significance for the pathophysiology of the immune response. TRP canonical channel 6 (TRPC6) is emerging as a functional element for the control of calcium currents in immune-committed cells and target tissues. In fact, TRPC6 influences leukocytes’ tasks such as transendothelial migration, chemotaxis, phagocytosis and cytokine release. TRPC6 also modulates the sensitivity of immune cells to apoptosis and influences tissue susceptibility to ischemia-reperfusion injury and excitotoxicity. Here, we provide a view of the interactions between ion exchanges and inflammation with a focus on the pathogenesis of immune-mediated diseases and potential future therapeutic implications. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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15 pages, 281 KiB  
Review
Role of the TRPM4 Channel in Cardiovascular Physiology and Pathophysiology
by Chen Wang, Keiji Naruse and Ken Takahashi
Cells 2018, 7(6), 62; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7060062 - 15 Jun 2018
Cited by 31 | Viewed by 5754
Abstract
The transient receptor potential cation channel subfamily M member 4 (TRPM4) channel influences calcium homeostasis during many physiological activities such as insulin secretion, immune response, respiratory reaction, and cerebral vasoconstriction. This calcium-activated, monovalent, selective cation channel also plays a key role in cardiovascular [...] Read more.
The transient receptor potential cation channel subfamily M member 4 (TRPM4) channel influences calcium homeostasis during many physiological activities such as insulin secretion, immune response, respiratory reaction, and cerebral vasoconstriction. This calcium-activated, monovalent, selective cation channel also plays a key role in cardiovascular pathophysiology; for example, a mutation in the TRPM4 channel leads to cardiac conduction disease. Recently, it has been suggested that the TRPM4 channel is also involved in the development of cardiac ischemia-reperfusion injury, which causes myocardial infarction. In the present review, we discuss the physiological function of the TRPM4 channel, and assess its role in cardiovascular pathophysiology. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
20 pages, 1046 KiB  
Review
Remarkable Progress with Small-Molecule Modulation of TRPC1/4/5 Channels: Implications for Understanding the Channels in Health and Disease
by Aisling Minard, Claudia C. Bauer, David J. Wright, Hussein N. Rubaiy, Katsuhiko Muraki, David J. Beech and Robin S. Bon
Cells 2018, 7(6), 52; https://0-doi-org.brum.beds.ac.uk/10.3390/cells7060052 - 01 Jun 2018
Cited by 43 | Viewed by 6719
Abstract
Proteins of the TRPC family can form many homo- and heterotetrameric cation channels permeable to Na+, K+ and Ca2+. In this review, we focus on channels formed by the isoforms TRPC1, TRPC4 and TRPC5. We review evidence for [...] Read more.
Proteins of the TRPC family can form many homo- and heterotetrameric cation channels permeable to Na+, K+ and Ca2+. In this review, we focus on channels formed by the isoforms TRPC1, TRPC4 and TRPC5. We review evidence for the formation of different TRPC1/4/5 tetramers, give an overview of recently developed small-molecule TRPC1/4/5 activators and inhibitors, highlight examples of biological roles of TRPC1/4/5 channels in different tissues and pathologies, and discuss how high-quality chemical probes of TRPC1/4/5 modulators can be used to understand the involvement of TRPC1/4/5 channels in physiological and pathophysiological processes. Full article
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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