scholarly journals Gain-of-Function Mutations in the Transient Receptor Potential Channels TRPV1 and TRPA1: How Painful?

2014 ◽  
pp. S205-S213 ◽  
Author(s):  
S. BOUKALOVA ◽  
F. TOUSKA ◽  
L. MARSAKOVA ◽  
A. HYNKOVA ◽  
L. SURA ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Pain Syndrome ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Single Amino Acid ◽  
Voltage Sensitivity ◽  
Gain Of Function ◽  
Potential Channels ◽  
Transient Receptor

Gain-of-function (GOF) mutations in ion channels are rare events, which lead to increased agonist sensitivity or altered gating properties, and may render the channel constitutively active. Uncovering and following characterization of such mutants contribute substantially to the understanding of the molecular basis of ion channel functioning. Here we give an overview of some GOF mutants in polymodal ion channels specifically involved in transduction of painful stimuli – TRPV1 and TRPA1, which are scrutinized by scientists due to their important role in development of some pathological pain states. Remarkably, a substitution of single amino acid in the S4-S5 region of TRPA1 (N855S) has been recently associated with familial episodic pain syndrome. This mutation increases chemical sensitivity of TRPA1, but leaves the voltage sensitivity unchanged. On the other hand, mutations in the analogous region of TRPV1 (R557K and G563S) severely affect all aspects of channel activation and lead to spontaneous activity. Comparison of the effects induced by mutations in homologous positions in different TRP receptors (or more generally in other distantly related ion channels) may elucidate the gating mechanisms conserved during evolution.

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.

Astrocytic potassium and calcium channels as integrators of the inflammatory and ischemic CNS microenvironment

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Samantha Schmaul ◽  
Nicholas Hanuscheck ◽  
Stefan Bittner
Keyword(s):  
Ion Channels ◽  
Calcium Channels ◽  
Transient Receptor Potential ◽  
Expression Patterns ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Current Evidence ◽  
Brain State ◽  
Potential Channels ◽  
Transient Receptor

Abstract Astrocytes are key regulators of their surroundings by receiving and integrating stimuli from their local microenvironment, thereby regulating glial and neuronal homeostasis. Cumulating evidence supports a plethora of heterogenic astrocyte subpopulations that differ morphologically and in their expression patterns of receptors, transporters and ion channels, as well as in their functional specialisation. Astrocytic heterogeneity is especially relevant under pathological conditions. In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), morphologically distinct astrocytic subtypes were identified and could be linked to transcriptome changes during different disease stages and regions. To allow for continuous awareness of changing stimuli across age and diseases, astrocytes are equipped with a variety of receptors and ion channels allowing the precise perception of environmental cues. Recent studies implicate the diverse repertoire of astrocytic ion channels – including transient receptor potential channels, voltage-gated calcium channels, inwardly rectifying K+ channels, and two-pore domain potassium channels – in sensing the brain state in physiology, inflammation and ischemia. Here, we review current evidence regarding astrocytic potassium and calcium channels and their functional contribution in homeostasis, neuroinflammation and stroke.

scholarly journals Familial trigeminal neuralgia – a systematic clinical study with a genomic screen of the neuronal electrogenisome

Cephalalgia ◽  
2020 ◽  
Vol 40 (8) ◽  
pp. 767-777 ◽  
Author(s):  
Giulia Di Stefano ◽  
Jun-Hui Yuan ◽  
Giorgio Cruccu ◽  
Stephen G Waxman ◽  
Sulayman D Dib-Hajj ◽  
...  
Keyword(s):  
Ion Channels ◽  
Trigeminal Neuralgia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Gap Junction Channels ◽  
Whole Exome ◽  
Genes Encoding ◽  
Potential Channels ◽  
Transient Receptor

Objective This cross-sectional study examined, for the first time, a large cohort of patients with trigeminal neuralgia, to ascertain the occurrence of familial cases, providing a systematic description of clinical features of familial disease. Since there is evidence linking hyperexcitability of trigeminal ganglion neurons to trigeminal neuralgia, we also carried out an exploratory genetic analysis of the neuronal electrogenisome in these patients. Methods We recorded familial occurrence by systematically interviewing all patients with a definite diagnosis of classical or idiopathic trigeminal neuralgia. We found 12 occurrences of trigeminal neuralgia with positive family history out of 88 enrolled patients. Whole-exome sequencing was carried out in 11 patients. We concentrated on the genetic variants within a 173-gene panel, comprising channel genes encoding sodium, potassium, calcium, chloride, transient receptor potential channels, and gap junction channels. Gene expression profiles were based on published RNA sequencing datasets of rodent/human trigeminal ganglia tissues, with a focus on genes related to neuronal excitability. Results In patients with familial trigeminal neuralgia, pain was more often located in the right, second division. All patients reported triggers. Four patients experienced concomitant continuous pain. Whole-exome sequencing analysis within the trigeminal ganglion electrogenisome identified 41 rare variants in ion channels, consisting of variants in sodium channels (6), potassium channels (10), chloride channels (5), calcium channels (7), transient receptor potential channels (12), and gap junction channels (1). In one patient, a previously profiled gain-of-function mutation in SCN10A (Nav1.8 p.Ala1304Thr), previously reported in painful neuropathy, was found; this variant was not present in unaffected siblings. Conclusions Our results suggest that familial occurrence of trigeminal neuralgia is more common than previously considered. Although our results demonstrate variants in genes encoding voltage-gated ion channels and transient receptor potential channels within these patients, further study will be needed to determine their roles in the pathogenesis of trigeminal neuralgia.

scholarly journals Redox and trace metal regulation of ion channels in the pain pathway

2015 ◽  
Vol 470 (3) ◽  
pp. 275-280 ◽  
Author(s):  
J. Grayson Evans ◽  
Slobodan M. Todorovic
Keyword(s):  
Ion Channels ◽  
Trace Metal ◽  
Redox Regulation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Pain Pathway ◽  
Alternative Means ◽  
Potential Channels ◽  
Transient Receptor

Given the clinical significance of pain disorders and the relative ineffectiveness of current therapeutics, it is important to identify alternative means of modulating nociception. The most obvious pharmacological targets are the ion channels that facilitate nervous transmission from pain sensors in the periphery to the processing regions within the brain and spinal cord. In order to design effective pharmacological tools for this purpose, however, it is first necessary to understand how these channels are regulated. A growing area of research involves the investigation of the role that trace metals and endogenous redox agents play in modulating the activity of a diverse group of ion channels within the pain pathway. In the present review, the most recent literature concerning trace metal and redox regulation of T-type calcium channels, NMDA (N-methyl-D-aspartate) receptors, GABAA (γ-aminobutyric acid A) receptors and TRP (transient receptor potential) channels are described to gain a comprehensive understanding of the current state of the field as well as to provide a basis for future thought and experimentation.

scholarly journals Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels

2022 ◽  
Vol 12 ◽  
Author(s):  
Wayland W. L. Cheng ◽  
Mark J. Arcario ◽  
John T. Petroff
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Binding Sites ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Lipid Binding ◽  
Transient Receptor Potential Channels ◽  
Allosteric Modulators ◽  
Potential Channels ◽  
Transient Receptor

Lipids modulate the function of many ion channels, possibly through direct lipid-protein interactions. The recent outpouring of ion channel structures by cryo-EM has revealed many lipid binding sites. Whether these sites mediate lipid modulation of ion channel function is not firmly established in most cases. However, it is intriguing that many of these lipid binding sites are also known sites for other allosteric modulators or drugs, supporting the notion that lipids act as endogenous allosteric modulators through these sites. Here, we review such lipid-drug binding sites, focusing on pentameric ligand-gated ion channels and transient receptor potential channels. Notable examples include sites for phospholipids and sterols that are shared by anesthetics and vanilloids. We discuss some implications of lipid binding at these sites including the possibility that lipids can alter drug potency or that understanding protein-lipid interactions can guide drug design. Structures are only the first step toward understanding the mechanism of lipid modulation at these sites. Looking forward, we identify knowledge gaps in the field and approaches to address them. These include defining the effects of lipids on channel function in reconstituted systems using asymmetric membranes and measuring lipid binding affinities at specific sites using native mass spectrometry, fluorescence binding assays, and computational approaches.

scholarly journals Role of transient receptor potential channels in regulating spermatozoa functions: A mini-review

2018 ◽  
pp. 1618-1623 ◽  
Author(s):  
Akshay Kumar ◽  
Abhishek Kumar Mishra ◽  
Dilip Kumar Swain ◽  
Vijay Singh ◽  
Sarvajeet Yadav ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Sperm Function ◽  
Calcium Dependent ◽  
Potential Channels ◽  
Transient Receptor

Flagellar navigation along the genital tract of male and female in spermatozoa is accomplished through a number of biological, physiological, biochemical, and electrophysiological alterations in spermatozoa. These alterations are highly precise, dynamic, and regulated through a number of ion channels along with their associated pathways. Beating of flagella along with intracellular metabolism of spermatozoa is associated with fluxing of Ca++ as well as release of Ca++ from different sources. Calcium fluxing through the spermatozoa is mediated through sperm-specific calcium channel and also through transient receptor potential (TRP) channels which are diversified multifamily of ion channels which are activated through a number of extracellular agents such as pH, temperature, chemicals, and pathogens. Research has shown the dynamic role of TRP channels in regulating sperm functions such as sperm chemotaxis, rheotaxis, thermotaxis, and eventually fertilization. Diversified forms of TRP and their involvement in regulation of sperm function opens new horizons of understanding of the sperm function and, in specific, issues related to infertility. This mini-review is an attempt to draw some insights into the action of TRP channels in regulating sperm fertility competence through both calcium-dependent and calcium-independent mechanisms.

scholarly journals Effects of Ginger and its Pungent Constituents on Transient Receptor Potential Channels

2017 ◽  
Vol 112 (3) ◽  
pp. 250a
Author(s):  
Young-Soo Kim ◽  
Chan Sik Hong ◽  
Sang Weon Lee ◽  
Joo Hyun Nam ◽  
Byung Joo Kim
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor
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