Transient Receptor Potential (TRP) Channels in the Brain: the Good and the Ugly

2012 ◽  
Vol 20 (3) ◽  
pp. 343-355 ◽  
Author(s):  
Bernd Nilius
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Sensory Function ◽  
Short Paper ◽  
The Novel ◽  
Cellular Functions ◽  
Transient Receptor ◽  
The Brain

The ‘transient receptor potential’ (TRP) multigene family encodes sixspan membrane proteins that function as ion channels in mostly tetrameric structures. Members of this family are conserved from yeast, worm, fly to invertebrate, vertebrate and man. These channels have been stigmatized to function only as cell sensors occupied by sensory function. It turns out that TRP channels fulfil a plethora of cellular functions, including non-sensory functions in our brain. This short paper will highlight the advent of novel ion channels in the brain serving different functions and being significantly involved in the genesis of multiple diseases. We will certainly witness a plethora of the novel roles of this protein family in physiological and pathophysiological functions in our central nervous system.

scholarly journals Calcium-permeable ion channels in the kidney

2016 ◽  
Vol 310 (11) ◽  
pp. F1157-F1167 ◽  
Author(s):  
Yiming Zhou ◽  
Anna Greka
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Transient Receptor Potential ◽  
Kidney Development ◽  
Kidney Diseases ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Cellular Functions ◽  
Potential Channels ◽  
Transient Receptor

Calcium ions (Ca2+) are crucial for a variety of cellular functions. The extracellular and intracellular Ca2+ concentrations are thus tightly regulated to maintain Ca2+ homeostasis. The kidney, one of the major organs of the excretory system, regulates Ca2+ homeostasis by filtration and reabsorption. Approximately 60% of the Ca2+ in plasma is filtered, and 99% of that is reabsorbed by the kidney tubules. Ca2+ is also a critical signaling molecule in kidney development, in all kidney cellular functions, and in the emergence of kidney diseases. Recently, studies using genetic and molecular biological approaches have identified several Ca2+-permeable ion channel families as important regulators of Ca2+ homeostasis in kidney. These ion channel families include transient receptor potential channels (TRP), voltage-gated calcium channels, and others. In this review, we provide a brief and systematic summary of the expression, function, and pathological contribution for each of these Ca2+-permeable ion channels. Moreover, we discuss their potential as future therapeutic targets.

Transient receptor potential ion channels as participants in thermosensation and thermoregulation

2007 ◽  
Vol 292 (1) ◽  
pp. R64-R76 ◽  
Author(s):  
Michael J. Caterina
Keyword(s):  
Ion Channels ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Core Body Temperature ◽  
Expression Patterns ◽  
Receptor Potential ◽  
Genetic Ablation ◽  
Transient Receptor ◽  
Living Organisms

Living organisms must evaluate changes in environmental and internal temperatures to mount appropriate physiological and behavioral responses conducive to survival. Classical physiology has provided a wealth of information regarding the specialization of thermosensory functions among subclasses of peripheral sensory neurons and intrinsically thermosensitive neurons within the hypothalamus. However, until recently, the molecular mechanisms by which these cells carry out thermometry have remained poorly understood. The demonstration that certain ion channels of the transient receptor potential (TRP) family can be activated by increases or decreases in ambient temperature, along with the recognition of their heterogeneous expression patterns and heterogeneous temperature sensitivities, has led investigators to evaluate these proteins as candidate endogenous thermosensors. Much of this work has involved one specific channel, TRP vanilloid 1 (TRPV1), which is both a receptor for capsaicin and related pungent vanilloid compounds and a “heat receptor,” capable of directly depolarizing neurons in response to temperatures >42°C. Evidence for a contribution of TRPV1 to peripheral thermosensation has come from pharmacological, physiological, and genetic approaches. In contrast, although capsaicin-sensitive mechanisms clearly influence core body temperature regulation, the specific contribution of TRPV1 to this process remains a matter of debate. Besides TRPV1, at least six additional thermally sensitive TRP channels have been identified in mammals, and many of these also appear to participate in thermosensation. Moreover, the identification of invertebrate TRP channels, whose genetic ablation alters thermally driven behaviors, makes it clear that thermosensation represents an evolutionarily conserved role of this ion channel family.

scholarly journals Deciphering the interactions of SARS-CoV-2 proteins with human ion channels using machine learning-based method

2021 ◽  
Author(s):  
Nupur S. Munjal ◽  
Dikscha Sapra ◽  
Abhishek Goyal ◽  
K.T. Shreya Parthasarathi ◽  
Akhilesh Pandey ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ion Channels ◽  
Gap Junction ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Cation Channel ◽  
Ppi Networks ◽  
Junction Protein ◽  
Transient Receptor

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the worldwide COVID-19 pandemic which began in 2019. It has a high transmission rate and pathogenicity leading to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning (ML)-based algorithms are providing higher accuracy for host-SARS-CoV-2 protein-protein interactions (PPIs). In this study, predictions of PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were performed using PPI-MetaGO algorithm. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% Matthews correlation coefficient (MCC) score and 84.09% F1 score. Thereafter, PPI networks of SARSCoV-2 proteins with HICs were generated. Furthermore, biological pathway analysis of HICs interacting with SARS-CoV-2 proteins showed the involvement of six pathways, namely inflammatory mediator regulation of transient receptor potential (TRP) channels, insulin secretion, renin secretion, gap junction, taste transduction and apelin signaling pathway. Our analysis suggests that transient receptor potential cation channel subfamily M member 4 (TRPM4), transient receptor potential cation channel subfamily A member 1 (TRPA1), gap junction protein alpha 1 (GJA1), potassium calcium-activated channel subfamily N member 4 (KCNN4), acid sensing ion channel subunit 1 (ASIC1) and inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) could serve as an initial set to the experimentalists for further validation. Additionally, various US food and drug administration (FDA) approved drugs interacting with the potential HICs were also identified. The study also reinforcesthe drug repurposing approach for the development of host directed antiviral drugs.

scholarly journals PIRT the TRP Channel Regulating Protein Binds Calmodulin and Cholesterol-Like Ligands

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 478 ◽  
Author(s):  
Nicholas J. Sisco ◽  
Dustin D. Luu ◽  
Minjoo Kim ◽  
Wade D. Van Horn
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Transmembrane Helix ◽  
Receptor Potential ◽  
Outer Leaflet ◽  
Heat Sensor ◽  
Transient Receptor ◽  
Α Helix ◽  
Obesity And Cancer

Transient receptor potential (TRP) ion channels are polymodal receptors that have been implicated in a variety of pathophysiologies, including pain, obesity, and cancer. The capsaicin and heat sensor TRPV1, and the menthol and cold sensor TRPM8, have been shown to be modulated by the membrane protein PIRT (Phosphoinositide-interacting regulator of TRP). The emerging mechanism of PIRT-dependent TRPM8 regulation involves a competitive interaction between PIRT and TRPM8 for the activating phosphatidylinositol 4,5-bisphosphate (PIP2) lipid. As many PIP2 modulated ion channels also interact with calmodulin, we investigated the possible interaction between PIRT and calmodulin. Using microscale thermophoresis (MST), we show that calmodulin binds to the PIRT C-terminal α-helix, which we corroborate with a pull-down experiment, nuclear magnetic resonance-detected binding study, and Rosetta-based computational studies. Furthermore, we identify a cholesterol-recognition amino acid consensus (CRAC) domain in the outer leaflet of the first transmembrane helix of PIRT, and with MST, show that PIRT specifically binds to a number of cholesterol-derivatives. Additional studies identified that PIRT binds to cholecalciferol and oxytocin, which has mechanistic implications for the role of PIRT regulation of additional ion channels. This is the first study to show that PIRT specifically binds to a variety of ligands beyond TRP channels and PIP2.

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 Dysfunction of transient receptor potential ion channels as an important pathophysiological mechanism in asthma

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Oxana Yu. Kytikova ◽  
Tatyana P. Novgorodtseva ◽  
Yulia K. Denisenko ◽  
Marina V. Antonyuk ◽  
Tatyana A. Gvozdenko
Keyword(s):  
Ion Channels ◽  
Neurogenic Inflammation ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Bronchial Hyperreactivity ◽  
Pathophysiological Mechanism ◽  
Lung Pathology ◽  
Trp Ion Channels ◽  
Transient Receptor

Asthma is a chronic heterogeneous disease characterized by chronic inflammation and bronchial hyperreactivity. Neurogenic inflammation is one of the important causes of hyperreactivity. Dysfunction of transient receptor potential (TRP) ion channels underlies the development of neurogenic inflammation, bronchial hyperreactivity and respiratory symptoms of asthma such as bronchospasm and cough. TRP channels are expressed in the respiratory tract. Their activation is mediated by endogenous and exogenous factors involved in the pathogenesis of asthma. The study of functioning and regulation of TRP channels is relevant, as they could be important therapeutic targets for asthma. The aim of the review is to summarize modern ideas about the mechanisms of functioning and regulation of members of the TRP channel superfamily, the role of which in lung pathology and physiology are the best studied.

scholarly journals TRPM8 Channels and Dry Eye

2018 ◽  
Vol 11 (4) ◽  
pp. 125 ◽  
Author(s):  
Jee Yang ◽  
Edward Wei ◽  
Seong Kim ◽  
Kyung Yoon
Keyword(s):  
Foreign Body ◽  
Dry Eye ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Eye Disease ◽  
Chemical Irritation ◽  
Body Discomfort ◽  
Transient Receptor ◽  
The Brain

Transient receptor potential (TRP) channels transduce signals of chemical irritation and temperature change from the ocular surface to the brain. Dry eye disease (DED) is a multifactorial disorder wherein the eyes react to trivial stimuli with abnormal sensations, such as dryness, blurring, presence of foreign body, discomfort, irritation, and pain. There is increasing evidence of TRP channel dysfunction (i.e., TRPV1 and TRPM8) in DED pathophysiology. Here, we review some of this literature and discuss one strategy on how to manage DED using a TRPM8 agonist.

scholarly journals Opening TRPP2 (PKD2L1) requires the transfer of gating charges

2019 ◽  
Vol 116 (31) ◽  
pp. 15540-15549 ◽  
Author(s):  
Leo C. T. Ng ◽  
Thuy N. Vien ◽  
Vladimir Yarov-Yarovoy ◽  
Paul G. DeCaen
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Voltage Gated ◽  
State Dependent ◽  
Transient Receptor ◽  
Voltage Gated Ion Channels ◽  
Gating Charges ◽  
Gated Ion Channels

The opening of voltage-gated ion channels is initiated by transfer of gating charges that sense the electric field across the membrane. Although transient receptor potential ion channels (TRP) are members of this family, their opening is not intrinsically linked to membrane potential, and they are generally not considered voltage gated. Here we demonstrate that TRPP2, a member of the polycystin subfamily of TRP channels encoded by the PKD2L1 gene, is an exception to this rule. TRPP2 borrows a biophysical riff from canonical voltage-gated ion channels, using 2 gating charges found in its fourth transmembrane segment (S4) to control its conductive state. Rosetta structural prediction demonstrates that the S4 undergoes ∼3- to 5-Å transitional and lateral movements during depolarization, which are coupled to opening of the channel pore. Here both gating charges form state-dependent cation–π interactions within the voltage sensor domain (VSD) during membrane depolarization. Our data demonstrate that the transfer of a single gating charge per channel subunit is requisite for voltage, temperature, and osmotic swell polymodal gating of TRPP2. Taken together, we find that irrespective of stimuli, TRPP2 channel opening is dependent on activation of its VSDs.

scholarly journals Roles of TRP Channels in Neurological Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Rui Wang ◽  
Sheng Tu ◽  
Jianmin Zhang ◽  
Anwen Shao
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Receptor Potential ◽  
Physiological Processes ◽  
Neuroprotective Strategies ◽  
Transient Receptor ◽  
Physical And Chemical ◽  
The Brain

Transient receptor potential (TRP) proteins consist of a superfamily of cation channels that have been involved in diverse physiological processes in the brain as well as in the pathogenesis of neurological disease. TRP channels are widely expressed in the brain, including neurons and glial cells, as well as in the cerebral vascular endothelium and smooth muscle. Members of this channel superfamily show a wide variety of mechanisms ranging from ligand binding to voltage, physical, and chemical stimuli, implying the promising therapeutic potential of TRP in neurological diseases. In this review, we focus on the physiological functions of TRP channels in the brain and the pathological roles in neurological disorders to explore future potential neuroprotective strategies.

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