scholarly journals pH sensing in skin tumors: Methods to study the involvement of GPCRs, acid‐sensing ion channels and transient receptor potential vanilloid channels

2020 ◽  
Vol 29 (11) ◽  
pp. 1055-1061
Author(s):  
Judith A. Stolwijk ◽  
Lisa Sauer ◽  
Kirsten Ackermann ◽  
Anaïs Nassios ◽  
Thiha Aung ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Skin Tumors ◽  
Transient Receptor Potential Vanilloid ◽  
Ph Sensing ◽  
Acid Sensing Ion Channels ◽  
Transient Receptor

scholarly journals Role of Transient Receptor Potential and Acid-sensing Ion Channels in Peripheral Inflammatory Pain

2010 ◽  
Vol 112 (3) ◽  
pp. 729-741 ◽  
Author(s):  
John P. M. White ◽  
Mario Cibelli ◽  
Antonio Rei Fidalgo ◽  
Cleoper C. Paule ◽  
Faruq Noormohamed ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Ionotropic Receptors ◽  
Acid Sensing Ion Channels ◽  
Peripheral Pain ◽  
Transient Receptor

Pain originating in inflammation is the most common pathologic pain condition encountered by the anesthesiologist whether in the context of surgery, its aftermath, or in the practice of pain medicine. Inflammatory agents, released as components of the body's response to peripheral tissue damage or disease, are now known to be collectively capable of activating transient receptor potential vanilloid type 1, transient receptor potential vanilloid type 4, transient receptor potential ankyrin type 1, and acid-sensing ion channels, whereas individual agents may activate only certain of these ion channels. These ionotropic receptors serve many physiologic functions-as, indeed, do many of the inflammagens released in the inflammatory process. Here, we introduce the reader to the role of these ionotropic receptors in mediating peripheral pain in response to inflammation.

scholarly journals Evolution of acid nociception: ion channels and receptors for detecting acid

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190291 ◽  
Author(s):  
Luke A. Pattison ◽  
Gerard Callejo ◽  
Ewan St John Smith
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
G Protein Coupled Receptors ◽  
Transient Receptor Potential Vanilloid ◽  
Ionic Homeostasis ◽  
Acid Sensing Ion Channels ◽  
Transient Receptor ◽  
G Protein Coupled ◽  
Cold Pressure

Nociceptors, i.e. sensory neurons tuned to detect noxious stimuli, are found in numerous phyla of the Animalia kingdom and are often polymodal, responding to a variety of stimuli, e.g. heat, cold, pressure and chemicals, such as acid. Owing to the ability of protons to have a profound effect on ionic homeostasis and damage macromolecular structures, it is no wonder that the ability to detect acid is conserved across many species. To detect changes in pH, nociceptors are equipped with an assortment of different acid sensors, some of which can detect mild changes in pH, such as the acid-sensing ion channels, proton-sensing G protein-coupled receptors and several two-pore potassium channels, whereas others, such as the transient receptor potential vanilloid 1 ion channel, require larger shifts in pH. This review will discuss the evolution of acid sensation and the different mechanisms by which nociceptors can detect acid. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

scholarly journals Expression Profiles of ASIC1/2 and TRPV1/4 in Common Skin Tumors

2021 ◽  
Vol 22 (11) ◽  
pp. 6024
Author(s):  
Kirsten Ackermann ◽  
Susanne Wallner ◽  
Christoph Brochhausen ◽  
Stephan Schreml
Keyword(s):  
Cell Carcinoma ◽  
Transient Receptor Potential ◽  
Expression Profiles ◽  
Receptor Potential ◽  
Skin Tumors ◽  
Transient Receptor Potential Vanilloid ◽  
Tissue Samples ◽  
Acid Sensing Ion Channels ◽  
Common Skin ◽  
Transient Receptor

The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of ASIC1, ASIC2, TRPV1 and TRPV4 in malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and in nevus cell nevi (NCN). We conducted immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express ASIC1/2 and TRPV1/4. Striking results were that BCCs are often negative for ASIC2, while nearly all SCCs express this marker. Epidermal MM sometimes seem to lack ASIC1 in contrast to NCN. Dermal portions of MM show strong expression of TRPV1 more frequently than dermal NCN portions. Some NCN show a decreasing ASIC1/2 expression in deeper dermal tumor tissue, while MM seem to not lose ASIC1/2 in deeper dermal portions. ASIC1, ASIC2, TRPV1 and TRPV4 in skin tumors might be involved in tumor progression, thus being potential diagnostic and therapeutic targets.

scholarly journals Confined Dynamics of Water in Transmembrane Pore of TRPV1 Ion Channel

2019 ◽  
Vol 20 (17) ◽  
pp. 4285
Author(s):  
Yury A. Trofimov ◽  
Nikolay A. Krylov ◽  
Roman G. Efremov
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
3D Structure ◽  
Receptor Potential ◽  
Md Simulations ◽  
Transient Receptor Potential Vanilloid ◽  
Free Energy Barrier ◽  
Transmembrane Pores ◽  
Ion Conducting ◽  
Transient Receptor

Solvation effects play a key role in chemical and biological processes. The microscopic properties of water near molecular surfaces are radically different from those in the bulk. Furthermore, the behavior of water in confined volumes of a nanometer scale, including transmembrane pores of ion channels, is especially nontrivial. Knowledge at the molecular level of structural and dynamic parameters of water in such systems is necessary to understand the mechanisms of ion channels functioning. In this work, the results of molecular dynamics (MD) simulations of water in the pore and selectivity filter domains of TRPV1 (Transient Receptor Potential Vanilloid type 1) membrane channel are considered. These domains represent nanoscale volumes with strongly amphiphilic walls, where physical behavior of water radically differs from that of free hydration (e.g., at protein interfaces) or in the bulk. Inside the pore and filter domains, water reveals a very heterogeneous spatial distribution and unusual dynamics: It forms compact areas localized near polar groups of particular residues. Residence time of water molecules in such areas is at least 1.5 to 3 times larger than that observed for similar groups at the protein surface. Presumably, these water “blobs” play an important role in the functional activity of TRPV1. In particular, they take part in hydration of the hydrophobic TRPV1 pore by localizing up to six waters near the so-called “lower gate” of the channel and reducing by this way the free energy barrier for ion and water transport. Although the channel is formed by four identical protein subunits, which are symmetrically packed in the initial experimental 3D structure, in the course of MD simulations, hydration of the same amino acid residues of individual subunits may differ significantly. This greatly affects the microscopic picture of the distribution of water in the channel and, potentially, the mechanism of its functioning. Therefore, reconstruction of the full picture of TRPV1 channel solvation requires thorough atomistic simulations and analysis. It is important that the naturally occurring porous volumes, like ion-conducting protein domains, reveal much more sophisticated and fine-tuned regulation of solvation than, e.g., artificially designed carbon nanotubes.

scholarly journals Peripheral Mechanobiology of Touch—Studies on Vertebrate Cutaneous Sensory Corpuscles

2020 ◽  
Vol 21 (17) ◽  
pp. 6221 ◽  
Author(s):  
Ramón Cobo ◽  
Jorge García-Piqueras ◽  
Yolanda García-Mesa ◽  
Jorge Feito ◽  
Olivia García-Suárez ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Mechanical Stimulus ◽  
Nerve Fibers ◽  
Current Data ◽  
Acid Sensing Ion Channels ◽  
Low Threshold ◽  
Transient Receptor

The vertebrate skin contains sensory corpuscles that are receptors for different qualities of mechanosensitivity like light brush, touch, pressure, stretch or vibration. These specialized sensory organs are linked anatomically and functionally to mechanosensory neurons, which function as low-threshold mechanoreceptors connected to peripheral skin through Aβ nerve fibers. Furthermore, low-threshold mechanoreceptors associated with Aδ and C nerve fibers have been identified in hairy skin. The process of mechanotransduction requires the conversion of a mechanical stimulus into electrical signals (action potentials) through the activation of mechanosensible ion channels present both in the axon and the periaxonal cells of sensory corpuscles (i.e., Schwann-, endoneurial- and perineurial-related cells). Most of those putative ion channels belong to the degenerin/epithelial sodium channel (especially the family of acid-sensing ion channels), the transient receptor potential channel superfamilies, and the Piezo family. This review updates the current data about the occurrence and distribution of putative mechanosensitive ion channels in cutaneous mechanoreceptors including primary sensory neurons and sensory corpuscles.

scholarly journals Taste Receptors in the Gastrointestinal Tract. V. Acid sensing in the gastrointestinal tract

2007 ◽  
Vol 292 (3) ◽  
pp. G699-G705 ◽  
Author(s):  
Peter Holzer
Keyword(s):  
Gastrointestinal Tract ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Extracellular Ph ◽  
Taste Receptors ◽  
Acid Sensing Ion Channels ◽  
Transient Receptor ◽  
Physiological Values ◽  
Pore Domain

Luminal acidity is a physiological challenge in the foregut, and acidosis can occur throughout the gastrointestinal tract as a result of inflammation or ischemia. These conditions are surveyed by an elaborate network of acid-governed mechanisms to maintain homeostasis. Deviations from physiological values of extracellular pH are monitored by multiple acid sensors expressed by epithelial cells and sensory neurons. Acid-sensing ion channels are activated by moderate acidification, whereas transient receptor potential ion channels of the vanilloid subtype are gated by severe acidosis. Some ionotropic purinoceptor ion channels and two-pore domain background K+ channels are also sensitive to alterations of extracellular pH.

scholarly journals Role of Gangliosides in Peripheral Pain Mechanisms

2020 ◽  
Vol 21 (3) ◽  
pp. 1005 ◽  
Author(s):  
Péter Sántha ◽  
Ildikó Dobos ◽  
Gyöngyi Kis ◽  
Gábor Jancsó
Keyword(s):  
Ion Channels ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Membrane Receptors ◽  
Transient Receptor Potential Vanilloid ◽  
Pain Mechanisms ◽  
Novel Approach ◽  
Transient Receptor ◽  
Nociceptive Ion Channels

Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain.

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