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Kharen L Doyle, Carla Cunha, Yvonne Hort, Ramon Tasan, Günther Sperk, John Shine, Herbert Herzog
The mouse olfactory neuroepithelium (ON) is comprised of anatomically distinct populations of cells in separate regions; apical (sustentacular and microvillar), neuronal (olfactory sensory neurons) and basal (horizontal and globose basal cells). The existence of microvillar cells (MVCs) is well documented but their nature and function remains unclear. An important transcription factor for the differentiation of MVCs is Skn-1a, with loss of function of Skn-1a in mice resulting in a complete loss of Trpm-5 expressing MVCs, while olfactory sensory neuron differentiation is normal...
March 1, 2018: Neuropeptides
Nils J G Rorsman, Chau M Ta, Hannah Garnett, Pawel Swietach, Paolo Tammaro
BACKGROUND AND PURPOSE: Optogenetic control of electromechanical coupling in vascular smooth muscle cells (VSMCs) is emerging as a powerful research tool with potential applications in drug discovery and therapeutics. However, the precise ionic mechanisms involved in this control remain unclear. EXPERIMENTAL APPROACH: Cell imaging, patch-clamp electrophysiology, and muscle tension recordings were used to define these mechanisms over a wide range of light stimulations...
February 27, 2018: British Journal of Pharmacology
Amrita Samanta, Taylor E T Hughes, Vera Y Moiseenkova-Bell
Transient Receptor Potential (TRP) channels are evolutionarily conserved integral membrane proteins. The mammalian TRP superfamily of ion channels consists of 28 cation permeable channels that are grouped into six subfamilies based on sequence homology (Fig. 6.1). The canonical TRP (TRPC) subfamily is known for containing the founding member of mammalian TRP channels. The vanilloid TRP (TRPV) subfamily has been extensively studied due to the heat sensitivity of its founding member. The melastatin-related TRP (TRPM) subfamily includes some of the few known bi-functional ion channels, which contain functional enzymatic domains...
2018: Sub-cellular Biochemistry
J B Lindström, N T Pierce, M I Latz
Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences...
October 2017: Biological Bulletin
Chanhyung Bae, Andres Jara-Oseguera, Kenton J Swartz
No abstract text is available yet for this article.
January 12, 2018: Science
Hiroshi Eguchi, Akio Hiura, Hiroshi Nakagawa, Shunji Kusaka, Yoshikazu Shimomura
Recently, in vivo confocal microscopy is used to examine the human corneal nerve fibers morphology. Corneal nerve fiber architecture and its role are studied in healthy and pathological conditions. Corneal nerves of rats were studied by nonspecific acetylcholinesterase (NsAchE) staining. NsAchE-positive subepithelial (stromal) nerve fiber has been found to be insensitive to capsaicin. Besides, NsAchE-negative but capsaicin-sensitive subbasal nerve (leash) fibers formed thick mesh-like structure showing close interconnections and exhibit both isolectin B4- and transient receptor potential vanilloid channel 1- (TRPV1-) positive...
2017: BioMed Research International
Ying Yin, Mengyu Wu, Lejla Zubcevic, William F Borschel, Gabriel C Lander, Seok-Yong Lee
Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cryo-electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 ångstroms. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer...
January 12, 2018: Science
Paige A Winkler, Yihe Huang, Weinan Sun, Juan Du, Wei Lü
Ca2+ -activated, non-selective (CAN) ion channels sense increases of the intracellular Ca2+ concentration, producing a flux of Na+ and/or K+ ions that depolarizes the cell, thus modulating cellular Ca2+ entry. CAN channels are involved in cellular responses such as neuronal bursting activity and cardiac rhythm. Here we report the electron cryo-microscopy structure of the most widespread CAN channel, human TRPM4, bound to the agonist Ca2+ and the modulator decavanadate. Four cytosolic C-terminal domains form an umbrella-like structure with a coiled-coil domain for the 'pole' and four helical 'ribs' spanning the N-terminal TRPM homology regions (MHRs), thus holding four subunits in a crown-like architecture...
December 14, 2017: Nature
Jiangtao Guo, Ji She, Weizhong Zeng, Qingfeng Chen, Xiao-Chen Bai, Youxing Jiang
TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2 ) -modulated, non-selective cation channel that belongs to the family of melastatin-related transient receptor potential (TRPM) channels. Here we present the electron cryo-microscopy structures of the mouse TRPM4 channel with and without ATP. TRPM4 consists of multiple transmembrane and cytosolic domains, which assemble into a three-tiered architecture. The N-terminal nucleotide-binding domain and the C-terminal coiled-coil participate in the tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain and inhibits channel activity...
December 14, 2017: Nature
Lucía Alonso-Carbajo, Miklos Kecskes, Griet Jacobs, Andy Pironet, Ninda Syam, Karel Talavera, Rudi Vennekens
The human TRP protein family comprises a family of 27 cation channels with diverse permeation and gating properties. The common theme is that they are very important regulators of intracellular Ca(2+) signaling in diverse cell types, either by providing a Ca(2+) influx pathway, or by depolarising the membrane potential, which on one hand triggers the activation of voltage-gated Ca(2+) channels, and on the other limits the driving force for Ca(2+) entry. Here we focus on the role of these TRP channels in vascular smooth muscle and cardiac striated muscle...
September 2017: Cell Calcium
Frank J P Kühn, Winking Mathis, Kühn Cornelia, Daniel C Hoffmann, Andreas Lückhoff
The archetypal TRPM2-like channel of the sea anemone Nematostella vectensis is gated by ADPR like its human orthologue but additionally exhibits properties of other vertebrate TRPM channels. Thus it can help towards an understanding of gating and regulation of the whole subfamily. To elucidate further the role of Ca(2+) as a co-factor of ADPR, we exploited 2-aminoethyl diphenylborinate (2-APB), previously shown to exert either inhibitory or stimulatory effects on diverse TRPM channels, or both in a concentration-dependent manner...
August 3, 2017: Scientific Reports
Fangfang Li, Tim S Munsey, Asipu Sivaprasadarao
Rise in plasma free fatty acids (FFAs) represents a major risk factor for obesity-induced type 2 diabetes. Saturated FFAs cause a progressive decline in insulin secretion by promoting pancreatic β-cell death through increased production of reactive oxygen species (ROS). Recent studies have demonstrated that palmitate (a C16 -FFA)-induced rise in ROS causes β-cell death by triggering mitochondrial fragmentation, but the underlying mechanisms are unclear. Using the INS1-832/13 β-cell line, here we demonstrate that palmitate generates the ROS required for mitochondrial fission by activating NOX (NADPH oxidase)-2...
December 2017: Cell Death and Differentiation
Eric C Lin, Crescent L Combe, Sonia Gasparini
Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of GABAA receptor antagonists, stimulation of afferent fibers, terminating both at proximal and distal dendritic locations, initiated hyperexcitable bursts in layer V medial entorhinal neurons. We investigated the differential contribution of Ca(2+)-dependent mechanisms to the plateaus underlying these bursts at proximal and distal synapses...
2017: Frontiers in Cellular Neuroscience
Susanna Zierler, Sarah Hampe, Wiebke Nadolni
The immune system protects our body against foreign pathogens. However, if it overshoots or turns against itself, pro-inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, or diabetes develop. Ions, the most basic signaling molecules, shape intracellular signaling cascades resulting in immune cell activation and subsequent immune responses. Mutations in ion channels required for calcium signaling result in human immunodeficiencies and highlight those ion channels as valued targets for therapies against pro-inflammatory diseases...
November 2017: Cell Calcium
Hongyu Li
The transient receptor potential (TRP) ion channels are named after the discovery of the photo-transducted channels in Drosophila. TRPs, activated by various extracellular and intracellular stimuli, play a plethora of physiological and pathological roles. There are seven families of TRPs including TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), TRPML (mucolipin), and TRPN (Drosophila NOMPC) in mammals. In yeast, the eighth TRP family was recently identified and named as TRPY...
2017: Advances in Experimental Medicine and Biology
Byung Joo Kim, Chansik Hong
Transient receptor potential (TRP) proteins are a family of ion channels, which are responsible for a wide array of cellular functions. In particular, TRP melastatin type (TRPM) 7 is expressed everywhere and permeable to divalent cations such as Mg(2+) and Ca(2+). It contains a channel and a kinase domain. Recent studies indicate that activation of TRPM7 plays an important role in the growth and survival of gastric cancer cells. In this review, we describe and discuss the findings of recent studies that have provided novel insights of the relation between TRPM7 and gastric cancer...
June 2016: Integrative Medicine Research
Jesse P Negherbon, Karina Romero, D'Ann L Williams, Rafael E Guerrero-Preston, Thomas Hartung, Alan L Scott, Patrick N Breysse, William Checkley, Nadia N Hansel
This study sought to investigate if acute phase immune responses of whole blood from Peruvian children with controlled and uncontrolled asthma differed from children without asthma, following exposure to traffic-related particulate matter (TRPM). TRPM, including particulate matter from diesel combustion, has been shown to stimulate acute airway inflammation in individuals with and without asthma. For this study, a whole blood assay (WBA) was used to test peripheral whole blood samples from 27 children with asthma, and 12 without asthma...
2017: Frontiers in Pharmacology
Amit Joshi, Abhay Joshi, Hiren Patel, Dovenia Ponnoth, Grazia Stagni
Menthol is a naturally occurring terpene used as a penetration enhancer in topical and transdermal formulations. Literature shows a growing interest in menthol's interactions with the transient receptor potential melastatin 8. A decrease in extracellular Ca(2+) due to the activation of the transient receptor potential melastatin 8 receptor produces inhibition of E-cadherin expression that is responsible for cell-cell adhesion. Because calcium is present in the entire epidermis, the purpose of this study is to evaluate whether the aforementioned properties of menthol are also related to its penetration-enhancing effects...
July 2017: Journal of Pharmaceutical Sciences
Sang Weon Lee, Sung Jin Kim, Hyungwoo Kim, Dongki Yang, Hyun Jung Kim, Byung Joo Kim
Interstitial cells of Cajal (ICCs) function as pacemaker cells in the gastrointestinal (GI) tract and therefore, serve an important role in regulating GI motility. The effects of a species of plum (Prunus mume Siebold & Zucc.) on cultured ICC cluster-induced pacemaker potentials in the mouse small intestine were investigated, and the effects of a methanolic extract of Prunus mume (m-PM) on ICC pacemaker activities were examined using the whole-cell patch-clamp technique. ICC pacemaker membrane potentials were depolarized by m-PM in a concentration dependent manner in current clamp mode...
January 2017: Experimental and Therapeutic Medicine
Gülay Güleç Ceylan, Ebru Etem Önalan, Tuncay Kuloğlu, Gülten Aydoğ, İbrahim Keleş, Şenol Tonyali, Cavit Ceylan
Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities...
December 2016: Oncology Letters
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