scholarly journals Transient Receptor Potential Cation Channels in Disease

2007 ◽  
Vol 87 (1) ◽  
pp. 165-217 ◽  
Author(s):  
Bernd Nilius ◽  
Grzegorz Owsianik ◽  
Thomas Voets ◽  
John A. Peters
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Divalent Cations ◽  
Receptor Potential ◽  
Hereditary Diseases ◽  
Cation Channels ◽  
Cell Functions ◽  
Transient Receptor ◽  
Trp Genes ◽  
The Impact

The transient receptor potential (TRP) superfamily consists of a large number of cation channels that are mostly permeable to both monovalent and divalent cations. The 28 mammalian TRP channels can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are expressed in almost every tissue and cell type and play an important role in the regulation of various cell functions. Currently, significant scientific effort is being devoted to understanding the physiology of TRP channels and their relationship to human diseases. At this point, only a few channelopathies in which defects in TRP genes are the direct cause of cellular dysfunction have been identified. In addition, mapping of TRP genes to susceptible chromosome regions (e.g., translocations, breakpoint intervals, increased frequency of polymorphisms) has been considered suggestive of the involvement of these channels in hereditary diseases. Moreover, strong indications of the involvement of TRP channels in several diseases come from correlations between levels of channel expression and disease symptoms. Finally, TRP channels are involved in some systemic diseases due to their role as targets for irritants, inflammation products, and xenobiotic toxins. The analysis of transgenic models allows further extrapolations of TRP channel deficiency to human physiology and disease. In this review, we provide an overview of the impact of TRP channels on the pathogenesis of several diseases and identify several TRPs for which a causal pathogenic role might be anticipated.

scholarly journals Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1983
Author(s):  
Xingjuan Chen ◽  
Gagandeep Sooch ◽  
Isaac S. Demaree ◽  
Fletcher A. White ◽  
Alexander G. Obukhov
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Hereditary Diseases ◽  
Trpc Channels ◽  
Dependent Manner ◽  
Transient Receptor Potential Canonical ◽  
Cell Functions ◽  
Transient Receptor

Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1–7). TRPCs exhibit the highest protein sequence similarity to the Drosophila melanogaster TRP channels. Similar to Drosophila TRPs, TRPCs are localized to the plasma membrane and are activated in a G-protein-coupled receptor-phospholipase C-dependent manner. TRPCs may also be stimulated in a store-operated manner, via receptor tyrosine kinases, or by lysophospholipids, hypoosmotic solutions, and mechanical stimuli. Activated TRPCs allow the influx of Ca2+ and monovalent alkali cations into the cytosol of cells, leading to cell depolarization and rising intracellular Ca2+ concentration. TRPCs are involved in the continually growing number of cell functions. Furthermore, mutations in the TRPC6 gene are associated with hereditary diseases, such as focal segmental glomerulosclerosis. The most important recent breakthrough in TRPC research was the solving of cryo-EM structures of TRPC3, TRPC4, TRPC5, and TRPC6. These structural data shed light on the molecular mechanisms underlying TRPCs’ functional properties and propelled the development of new modulators of the channels. This review provides a historical overview of the major advances in the TRPC field focusing on the role of gene knockouts and pharmacological tools.

scholarly journals Taste the Pain: The Role of TRP Channels in Pain and Taste Perception

2020 ◽  
Vol 21 (16) ◽  
pp. 5929 ◽  
Author(s):  
Edwin Aroke ◽  
Keesha Powell-Roach ◽  
Rosario Jaime-Lara ◽  
Markos Tesfaye ◽  
Abhrarup Roy ◽  
...  
Keyword(s):  
Pain Perception ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Taste Perception ◽  
Therapeutic Interventions ◽  
Sensory Stimuli ◽  
Transient Receptor ◽  
Trp Genes

Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste–pain sensorial experiences are not fully understood. This article provides a narrative review of literature examining the role of TRP channels on taste and pain perception. Genomic variability in the TRPV1 gene has been associated with alterations in various pain conditions. Moreover, polymorphisms of the TRPV1 gene have been associated with alterations in salty taste sensitivity and salt preference. Studies of genetic variations in TRP genes or modulation of TRP pathways may increase our understanding of the shared biological mediators of pain and taste, leading to therapeutic interventions to treat many diseases.

scholarly journals Drosophila menthol sensitivity and the Precambrian origins of TRP-dependent chemosensation

2019 ◽  
Author(s):  
Nathaniel J. Himmel ◽  
Jamin M. Letcher ◽  
Akira Sakurai ◽  
Thomas R. Gray ◽  
Maggie N. Benson ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Topical Application ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Cation Channels ◽  
Growing Body ◽  
Sensitivity Studies ◽  
Transient Receptor ◽  
Class Iv

AbstractTransient receptor potential (TRP) cation channels are highly conserved, polymodal sensors which respond to a wide variety of stimuli. Perhaps most notably, TRP channels serve critical functions in nociception and pain. A growing body of evidence suggests that TRPM (Melastatin) and TRPA (Ankyrin) thermal and electrophile sensitivities predate the protostome-deuterostome split (>550 million years ago). However, TRPM and TRPA channels are also thought to detect modified terpenes (e.g., menthol). Although terpenoids like menthol are thought to be aversive and/or harmful to insects, mechanistic sensitivity studies have been largely restricted to chordates. Furthermore, it is unknown if TRP-menthol sensing is as ancient as thermal and/or electrophile sensitivity. Combining genetic, optical, electrophysiological, behavioural, and phylogenetic approaches, we tested the hypothesis that insect TRP channels play a conserved role in menthol sensing. We found that topical application of menthol to Drosophila melanogaster larvae elicits a Trpm- and TrpA1-dependent nocifensive rolling behaviour, which requires activation of Class IV nociceptor neurons. Further, in characterizing the evolution of TRP channels, we put forth the hypotheses that 3 previously undescribed TRPM channel clades (basal, αTRPM, and βTRPM), as well as TRPs with residues critical for menthol sensing, were present in ancestral bilaterians.

scholarly journals A TRiP Through the Roles of Transient Receptor Potential Cation Channels in Type 2 Upper Airway Inflammation

2021 ◽  
Vol 21 (3) ◽  
Author(s):  
Wout Backaert ◽  
Brecht Steelant ◽  
Peter W. Hellings ◽  
Karel Talavera ◽  
Laura Van Gerven
Keyword(s):  
Airway Inflammation ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Upper Airway ◽  
Receptor Potential ◽  
Cation Channels ◽  
Cellular Functions ◽  
Upper Airways ◽  
Transient Receptor

Abstract Purpose of Review Despite their high prevalence, the pathophysiology of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) remains unclear. Recently, transient receptor potential (TRP) cation channels emerged as important players in type 2 upper airway inflammatory disorders. In this review, we aim to discuss known and yet to be explored roles of TRP channels in the pathophysiology of AR and CRS with nasal polyps. Recent Findings TRP channels participate in a plethora of cellular functions and are expressed on T cells, mast cells, respiratory epithelial cells, and sensory neurons of the upper airways. In chronic upper airway inflammation, TRP vanilloid 1 is mostly studied in relation to nasal hyperreactivity. Several other TRP channels such as TRP vanilloid 4, TRP ankyrin 1, TRP melastatin channels, and TRP canonical channels also have important functions, rendering them potential targets for therapy. Summary The role of TRP channels in type 2 inflammatory upper airway diseases is steadily being uncovered and increasingly recognized. Modulation of TRP channels may offer therapeutic perspectives.

scholarly journals TRPM2 in the Brain: Role in Health and Disease

Cells ◽  
2018 ◽  
Vol 7 (7) ◽  
pp. 82 ◽  
Author(s):  
Giulia Sita ◽  
Patrizia Hrelia ◽  
Agnese Graziosi ◽  
Gloria Ravegnini ◽  
Fabiana Morroni
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Cell Functions ◽  
Neuroprotective Strategies ◽  
Health And Disease ◽  
Future Potential ◽  
Transient Receptor ◽  
Multiple Signaling ◽  
The Brain

Transient receptor potential (TRP) proteins have been implicated in several cell functions as non-selective cation channels, with about 30 different mammalian TRP channels having been recognized. Among them, TRP-melastatin 2 (TRPM2) is particularly involved in the response to oxidative stress and inflammation, while its activity depends on the presence of intracellular calcium (Ca2+). TRPM2 is involved in several physiological and pathological processes in the brain through the modulation of multiple signaling pathways. The aim of the present review is to provide a brief summary of the current insights of TRPM2 role in health and disease to focalize our attention on future potential neuroprotective strategies.

scholarly journals Drosophila menthol sensitivity and the Precambrian origins of transient receptor potential-dependent chemosensation

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190369 ◽  
Author(s):  
Nathaniel J. Himmel ◽  
Jamin M. Letcher ◽  
Akira Sakurai ◽  
Thomas R. Gray ◽  
Maggie N. Benson ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Cation Channels ◽  
Transient Receptor Potential Melastatin ◽  
Growing Body ◽  
Sensitivity Studies ◽  
Transient Receptor ◽  
Class Iv

Transient receptor potential (TRP) cation channels are highly conserved, polymodal sensors which respond to a wide variety of stimuli. Perhaps most notably, TRP channels serve critical functions in nociception and pain. A growing body of evidence suggests that transient receptor potential melastatin (TRPM) and transient receptor potential ankyrin (TRPA) thermal and electrophile sensitivities predate the protostome–deuterostome split (greater than 550 Ma). However, TRPM and TRPA channels are also thought to detect modified terpenes (e.g. menthol). Although terpenoids like menthol are thought to be aversive and/or harmful to insects, mechanistic sensitivity studies have been largely restricted to chordates. Furthermore, it is unknown if TRP-menthol sensing is as ancient as thermal and/or electrophile sensitivity. Combining genetic, optical, electrophysiological, behavioural and phylogenetic approaches, we tested the hypothesis that insect TRP channels play a conserved role in menthol sensing. We found that topical application of menthol to Drosophila melanogaster larvae elicits a Trpm - and TrpA1 -dependent nocifensive rolling behaviour, which requires activation of Class IV nociceptor neurons. Further, in characterizing the evolution of TRP channels, we put forth the hypotheses that three previously undescribed TRPM channel clades (basal, αTRPM and βTRPM), as well as TRPs with residues critical for menthol sensing, were present in ancestral bilaterians. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

scholarly journals TRP Channels in Digestive Tract Cancers

2020 ◽  
Vol 21 (5) ◽  
pp. 1877 ◽  
Author(s):  
Paulina Stokłosa ◽  
Anna Borgström ◽  
Sven Kappel ◽  
Christine Peinelt
Keyword(s):  
Digestive Tract ◽  
Drug Targets ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Divalent Cations ◽  
Receptor Potential ◽  
Selective Permeability ◽  
Candidate Drug ◽  
Transient Receptor

Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets.

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

2011 ◽  
Vol 110 (3) ◽  
pp. 789-798 ◽  
Author(s):  
Kaori Ono ◽  
Masako Tsukamoto-Yasui ◽  
Yoshiko Hara-Kimura ◽  
Naohiko Inoue ◽  
Yoshihito Nogusa ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Low Frequency ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Intragastric Administration ◽  
Brown Adipose ◽  
Reflex Arc ◽  
Transient Receptor

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

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