TRPM3

Calmodulin is a small protein that binds Ca2+ ions via four EF-hand motifs. The Ca2+ /calmodulin complex as well as Ca2+ -free calmodulin regulate the activities of numerous enzymes and ion channels. Here, we used genetic and pharmacological tools to study the functional role of calmodulin in regulating signal transduction of TRPM3 and TRPM8 channels. Both TRPM3 and TRPM8 are important regulators of thermosensation. Gene transcription triggered by stimulation of TRPM3 or TRPM8 channels was significantly impaired in cells expressing a calmodulin mutant with mutations in all four EF-hand Ca2+ binding motifs...

Transient receptor potential melastatin 3 (TRPM3) channels contribute to nodose afferent and brainstem nucleus tractus solitarii (nTS) activity. Exposure to short, sustained hypoxia (SH) and chronic intermittent hypoxia (CIH) enhances nTS activity, although the mechanisms are unknown. We hypothesized TRPM3 may contribute to increased neuronal activity in nTS-projecting nodose ganglia viscerosensory neurons, and its influence is elevated following hypoxia. Rats were exposed to either room air (normoxia), 24-h of 10 % O2 (SH), or CIH (episodic 6 % O2 for 10d)...

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) provides valuable insights into human islet cell types and their corresponding stable gene expression profiles. However, this approach requires cell dissociation that complicates its utility in vivo. On the other hand, single-nucleus RNA sequencing (snRNA-seq) has compatibility with frozen samples, elimination of dissociation-induced transcriptional stress responses, and affords enhanced information from intronic sequences that can be leveraged to identify pre-mRNA transcripts...

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemotherapy and has significant negative consequences on the quality of life of survivors. Current treatment options for CIPNP are limited and unsatisfactory. TRPM3 is a calcium-permeable ion channel functionally expressed in peripheral sensory neurons involved in the detection of thermal stimuli...

BACKGROUND: Oxylipins are inflammatory biomarkers derived from omega-3 and-6 fatty acids implicated in inflammatory diseases but have not been studied in a genome-wide association study (GWAS). The aim of this study was to identify genetic loci associated with oxylipins and oxylipin profiles to identify biologic pathways and therapeutic targets for oxylipins. METHODS: We conducted a GWAS of plasma oxylipins in 316 participants in the Diabetes Autoimmunity Study in the Young (DAISY)...

Neurosteroids are important endogenous modulators of GABAA receptor-mediated neurotransmission within the CNS and play a vital role in maintaining normal healthy brain function. Research has mainly focussed on neurosteroids such as allopregnanolone and tetrahydro-deoxycorticosterone (THDOC) which are allosteric potentiators of GABAA receptors, whilst the sulphated steroids, including pregnenolone sulphate (PS), which inhibit GABAA receptor function, have been relatively neglected. Importantly, a full description of PS effects on inhibitory synaptic transmission, at concentrations that are expected to inhibit postsynaptic GABAA receptors, is lacking...

Developmental and epileptic encephalopathy (DEE) with continuous spike-and-wave activation in sleep (CSWS) or DEE-SWAS is an age-dependent disease, often accompanied by a decline in cognitive abilities. Early successful treatment of CSWS is associated with a better cognitive outcome. We retrospectively analyzed the clinical, electrophysiological, radiological, and genetic data of children with DEE-SWAS associated with melastatin-related transient receptor type 3 gene (TRPM3) missense variants. We report two unrelated children with pharmaco-resistant DEE-SWAS and developmental delay/regression and different heterozygous de novo missense variants in the TRPM3 gene (NM_001366145...

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

TRPM3 is an ion channel that is highly expressed in nociceptive neurons and plays a key role in pain perception. In the presence of the endogenous TRPM3 ligand, pregnenolone sulfate (PS), the antifungal compound clotrimazole (Clt) augments Ca2+ signaling and opens a non-canonical pore, permeable to Na+ , which aggravates TRPM3-induced pain. To date, little is known about structural features that govern the Clt modulatory effect of TRPM3. Here, we synthesized and evaluated several Clt analogues in order to gain insights into their structure-activity relationship...

OBJECTIVES: We aimed at identifying the role of transient receptor potential (TRP) channels in pterygium. METHODS: Based on microarray data GSE83627 and GSE2513, differentially expressed genes (DEGs) were screened and 20 hub genes were selected. After gene correlation analysis, 5 TRP-related genes were obtained and functional analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Multifactor regulatory network including mRNA, microRNAs (miRNAs) and transcription factors (TFs) was constructed...

BACKGROUND: and purpose: Phenazopyridine (PAP) is an over-the-counter drug widely used to provide symptomatic relief of bladder pain in conditions such as cystitis or bladder pain syndrome (BPS). Whereas the analgesic effect of PAP has been attributed to a local effect on the mucosa of the lower urinary tract (LUT), the molecular targets of PAP remain unknown. We investigated the effect of PAP on pain-related Transient Receptor Potential (TRP) channels expressed in sensory neurons that innervate the bladder wall...

TRPM3 is a temperature- and neurosteroid-sensitive plasma membrane cation channel expressed in a variety of neuronal and non-neuronal cells. Recently, rare de novo variants in TRPM3 were identified in individuals with developmental and epileptic encephalopathy (DEE), but the link between TRPM3 activity and neuronal disease remains poorly understood. We previously reported that two disease-associated variants in TRPM3 lead to a gain of channel function (Van Hoeymissen et al., 2020; Zhao et al., 2020). Here, we report a further ten patients carrying one of seven additional heterozygous TRPM3 missense variants...

G-protein coupled receptors (GPCRs) govern the physiological response to stimuli by modulating the activity of downstream effectors, including ion channels. TRPM3 is an ion channel inhibited by GPCRs through direct interaction with G protein (Gβγ) released upon their activation. This GPCR-TRPM3 signaling pathway contributes to the analgesic effect of morphine. Here, we characterized Gβγ inhibition of TRPM3 using electrophysiology and single particle cryo-electron microscopy (cryo-EM)...

Introduction: Mutations and misfolding of membrane proteins are associated with various disorders, hence they make suitable targets in proteomic studies. However, extraction of membrane proteins is challenging due to their low abundance, stability, and susceptibility to protease degradation. Given the limitations in existing protocols for membrane protein extraction, the aim of this investigation was to develop a protocol for a high yield of membrane proteins for isolated Natural Killer (NK) cells. This will facilitate genetic analysis of membrane proteins known as transient receptor potential melastatin 3 (TRPM3) ion channels in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) research...

Transient Receptor Potential Melastatin 3 (TRPM3) is a heat-activated ion channel expressed in peripheral sensory neurons and the central nervous system. TRPM3 activity depends on the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ], but the molecular mechanism of activation by PI(4,5)P2 is not known. As no experimental structure of TRPM3 is available, we built a homology model of the channel in complex with PI(4,5)P2 via molecular modeling. We identified putative contact residues for PI(4,5)P2 in the pre-S1 segment, the S4-S5 linker, and the proximal C-terminal TRP-domain...

This study aimed to test for the possible antinociceptive effect of the naturally occurring terpene citral in rodent models of acute and chronic orofacial pain and to test for the possible involvement of transient receptor potential (TRP) channels in this effect. Acute nociceptive behavior was induced in one series of experiments by administering formalin, cinnamaldehyde, menthol or capsaicin to the upper lip. Nociceptive behavior was assessed by orofacial rubbing, and the effects of pre-treatment with citral (0...

Coronavirus disease 2019 (COVID-19) seriously threatens human health and has been disseminated worldwide. Although there are several treatments for COVID-19, its control is currently suboptimal. Therefore, the development of novel strategies to treat COVID-19 is necessary. Ion channels are located on the membranes of all excitable cells and many intracellular organelles and are key components involved in various biological processes. They are a target of interest when searching for drug targets. This study aimed to reveal the relevant molecular features of ion channel genes in COVID-19 based on bioinformatic analyses...

Transient receptor potential (TRP) channels are cation channels that play a regulatory role in pain and thermosensation, insulin secretion, and neurotransmission. It has been proposed that activation of TRP channels requires phosphatidylinositol 4,5-bisphosphate, the major substrate for phospholipase C (PLC). We investigated whether inhibition of PLCβ has an impact on TRP channel signaling. A genetic approach was used to avoid off-target effects observed when using a pharmacological PLCβ inhibitor. In this study, we show that expression of PLCβ1ct and PLCβ3ct, truncated forms of PLCβ1 or PLCβ3 that contain the C-terminal membrane binding domains, almost completely blocked the signal transduction of a Gαq-coupled designer receptor, including the phosphorylation of ERK1/2...