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Juan R Martinez-Galan, Ana Verdejo, Elena Caminos
Disturbances in calcium homeostasis due to canonical transient receptor potential (TRPC) and/or store-operated calcium (SOC) channels can play a key role in a large number of brain disorders. TRPC channels are plasma membrane cation channels included in the transient receptor potential (TRP) superfamily. The most widely distributed member of the TRPC subfamily in the brain is TRPC1, which is frequently linked to group I metabotropic glutamate receptors (mGluRs) and to the components of SOC channels. Proposing TRPC/SOC channels as a therapeutic target in neurological diseases previously requires a detailed knowledge of the distribution of such molecules in the brain...
2018: Frontiers in Neuroanatomy
Antonio Reboreda, Frederik M Theissen, Maria Valero-Aracama, Alberto Arboit, Mihaela A Corbu, Motoharu Yoshida
Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information. In this review, we will focus on the role of transient receptor potential canonical (TRPC) channels as a mechanism underlying persistent firing. Many years of in vitro work have been suggesting a crucial role of TRPC channels in working memory and temporal association tasks...
March 1, 2018: Behavioural Brain Research
Jun Wu, Daniel Ryskamp, Lutz Birnbaumer, Ilya Bezprozvanny
BACKGROUND: Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. We previously discovered that mutant Huntingtin sensitizes type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) to InsP3. This causes calcium leakage from the endoplasmic reticulum (ER) and a compensatory increase in neuronal store-operated calcium (nSOC) entry. We previously demonstrated that supranormal nSOC leads to synaptic loss in striatal medium spiny neurons (MSNs) in YAC128 HD mice...
2018: Journal of Huntington's Disease
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
Jessica Morand, Claire Arnaud, Jean-Louis Pepin, Diane Godin-Ribuot
We investigated the effects of intermittent hypoxia (IH), such as that encountered in severe obstructive sleep apnea (OSA) patients, on the development and severity of myocardial ischemia-related ventricular arrhythmias. Rats were exposed to 14 days of IH (30 s at 5%O 2 and 30 s at 21%O 2 , 8 h·day -1 ) or normoxia (N, similar air-air cycles) and submitted to a 30-min coronary ligature. Arterial blood pressure (BP) and ECG were recorded for power spectral analysis, ECG interval measurement and arrhythmia quantification...
February 14, 2018: Scientific Reports
Akiko Kojima, Yutaka Fukushima, Yuki Ito, Wei-Guang Ding, Hirotoshi Kitagawa, Hiroshi Matsuura
Reperfusion of ischemic myocardium is accompanied by intracellular Ca overload, leading to cardiac dysfunction. However, the mechanisms underlying intracellular Ca overload have yet to be fully elucidated. The mechanism may involve the activation of store-operated Ca entry, which is primarily mediated through the transient receptor potential canonical (TRPC) channels. The present study was undertaken to examine the possible involvement of TRPC channels in the development of contractile dysfunction associated with reperfusion of ischemic myocardium using a mouse heart model...
January 30, 2018: Journal of Cardiovascular Pharmacology
Stefan Just, Bertrand L Chenard, Angelo Ceci, Timothy Strassmaier, Jayhong A Chong, Nathaniel T Blair, Randall J Gallaschun, Donato Del Camino, Susan Cantin, Marc D'Amours, Christian Eickmeier, Christopher M Fanger, Carsten Hecker, David P Hessler, Bastian Hengerer, Katja S Kroker, Sam Malekiani, Robert Mihalek, Joseph McLaughlin, Georg Rast, JoAnn Witek, Achim Sauer, Christopher R Pryce, Magdalene M Moran
BACKGROUND: Forty million adults in the US suffer from anxiety disorders, making these the most common forms of mental illness. Transient receptor potential channel canonical subfamily (TRPC) members 4 and 5 are non-selective cation channels highly expressed in regions of the cortex and amygdala, areas thought to be important in regulating anxiety. Previous work with null mice suggests that inhibition of TRPC4 and TRPC5 may have anxiolytic effects. HC-070 IN VITRO: To assess the potential of TRPC4/5 inhibitors as an avenue for treatment, we invented a highly potent, small molecule antagonist of TRPC4 and TRPC5 which we call HC-070...
2018: PloS One
Robin Sachdeva, Andrea Schlotterer, Dagmar Schumacher, Christin Matka, Ilka Mathar, Nadine Dietrich, Rebekka Medert, Ulrich Kriebs, Jihong Lin, Peter Nawroth, Lutz Birnbaumer, Thomas Fleming, Hans-Peter Hammes, Marc Freichel
OBJECTIVE: Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6-/- compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy. METHODS: We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types...
January 5, 2018: Molecular Metabolism
Stéphanie Ratté, Sergei Karnup, Steven A Prescott
Persistent spiking - the continuation of spiking after a stimulus ends - is thought to support working memory. Muscarinic receptor activation enables persistent spiking among synaptically isolated pyramidal neurons in anterior cingulate cortex (ACC) but a detailed characterization of that spiking is lacking and the underlying mechanisms remain unclear. Here we show that the rate of persistent spiking in ACC neurons is insensitive to the intensity and number of triggers but can be modulated by injected current, and that persistent spiking can resume after several seconds of hyperpolarization-imposed quiescence...
January 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
Claudio F Perez, Jose M Eltit, Jose R Lopez, Dóra Bodnár, Angela F Dulhunty, Shouvik Aditya, Marco G Casarotto
Malignant hyperthermia (MH) susceptibility has been recently linked to a novel variant of β1a subunit of the dihydropyridine receptor (DHPR), a channel essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of the mutant variant V156A on the structure/function of DHPR β1a subunit and assess its role on Ca2+ metabolism of cultured myotubes. Using differential scanning fluorimetry, we show that mutation V156A causes a significant reduction in thermal stability of the Src homology 3/guanylate kinase core domain of β1a subunit...
March 1, 2018: American Journal of Physiology. Cell Physiology
Dariia Dryn, Jialie Luo, Mariia Melnyk, Alexander Zholos, Hongzhen Hu
Gastrointestinal tract motility may be demoted significantly after surgery operations at least in part due to anaesthetic agents, but there is no comprehensive explanation of the molecular mechanism(s) of such adverse effects. Anesthetics are known to interact with various receptors and ion channels including several subtypes of transient receptor potential (TRP) channels. Two members of the canonical subfamily of TRP channels (TRPC), TRPC4 and TRPC6 are Ca2+ -permeable cation channels involved in visceral smooth muscle contractility induced by acetylcholine, the primary excitatory neurotransmitter in the gut...
February 5, 2018: European Journal of Pharmacology
Xavier Fioramonti, Chloé Chrétien, Corinne Leloup, Luc Pénicaud
The hypothalamus have been recognized for decades as one of the major brain centers for the control of energy homeostasis. This area contains specialized neurons able to detect changes in nutrients level. Among them, glucose-sensing neurons use glucose as a signaling molecule in addition to its fueling role. In this review we will describe the different sub-populations of glucose-sensing neurons present in the hypothalamus and highlight their nature in terms of neurotransmitter/neuropeptide expression. This review will particularly discuss whether pro-opiomelanocortin (POMC) neurons from the arcuate nucleus are directly glucose-sensing...
2017: Frontiers in Physiology
Katarina Ondrusova, Mohammad Fatehi, Amy Barr, Zofia Czarnecka, Wentong Long, Kunimasa Suzuki, Scott Campbell, Koenraad Philippaert, Matthew Hubert, Edward Tredget, Peter Kwan, Nicolas Touret, Martin Wabitsch, Kevin Y Lee, Peter E Light
Subcutaneous white adipose tissue (scWAT) is the major fat depot in humans and is a central player in regulating whole body metabolism. Skin exposure to UV wavelengths from sunlight is required for Vitamin D synthesis and pigmentation, although it is plausible that longer visible wavelengths that penetrate the skin may regulate scWAT function. In this regard, we discovered a novel blue light-sensitive current in human scWAT that is mediated by melanopsin coupled to transient receptor potential canonical cation channels...
November 27, 2017: Scientific Reports
Linting Wei, Yan Du, Lining Jia, Xiaotao Ma, Zhao Chen, Jiamei Lu, Lifang Tian, Zhaoyang Duan, Fengming Dong, Zhian Lv, Ganglian Yao, Rongguo Fu, Li Wang
BACKGROUND/AIMS: FK506 is an immunosuppressive drug and a calcineurin inhibitor that has been widely used in kidney disease in recent years. FK506 shows a wide range of biological and pharmaceutical effects; however, the mechanism of its anti- proliferative effect has not been well elucidated. An IgA nephropathy (IgAN) model was used to generate a mesangial cell proliferation model. This study aims to examine the effect of FK506 on IgAN rats and the underlying mechanisms. METHODS: Hematuria, proteinuria and renal function were measured...
2017: Kidney & Blood Pressure Research
Geromy G Moore, Rodrigo A Olarte, Bruce W Horn, Jacalyn L Elliott, Rakhi Singh, Carolyn J O'Neal, Ignazio Carbone
Aflatoxins produced by several species in Aspergillus section Flavi are a significant problem in agriculture and a continuous threat to human health. To provide insights into the biology and global population structure of species in section Flavi, a total of 1,304 isolates were sampled across six species (A. flavus, A. parasiticus, A. nomius, A. caelatus, A. tamarii, and A. alliaceus) from single fields in major peanut-growing regions in Georgia (USA), Australia, Argentina, India, and Benin (Africa). We inferred maximum-likelihood phylogenies for six loci, both combined and separately, including two aflatoxin cluster regions (aflM/alfN and aflW/aflX) and four noncluster regions (amdS, trpC, mfs and MAT), to examine population structure and history...
November 2017: Ecology and Evolution
Pramod Sukumaran, Yuyang Sun, Neil Antonson, Brij B Singh
Alterations in Ca(2+) homeostasis affect neuronal survival. However, the identity of Ca(2+) channels and the mechanisms underlying neurotoxin-induced neuronal degeneration are not well understood. In this study, the dopaminergic neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl -4-phenylpyridium ions (MPP(+)/MPTP), which mimic Parkinson's disease (PD), induced neuronal degeneration by decreasing store-mediated Ca(2+) entry. The function of the transient receptor potential canonical (TRPC)-1 channel was decreased upon exposure to the neurotoxins, followed by a decrease in TRPC1 expression...
November 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Li-Fen Zhou, Qing-Zi Chen, Chun-Tao Yang, Zhao-Di Fu, Shen-Ting Zhao, Yan Chen, Shu-Ni Li, Li Liao, Yu-Bo Zhou, Jian-Rong Huang, Jian-Hua Li
Transient receptor potential canonical (TRPC) channels are currently an emerging target for airway disorders. Recent evidences have indicated that TRPC6 as a member of the TRPC family plays an important role in airway inflammation, but its precise function in bronchial epithelial cells remains unclear. The aim of this study was to investigate the role of TRPC6 in TLR4-mediated inflammation in human bronchial epithelial cells stimulated by endotoxin (lipopolysaccharide, LPS). Hyp9 is a simplified phloroglucinol derivative of Hyperforin which highly selective activates TRPC6 channels...
November 15, 2017: American Journal of Physiology. Cell Physiology
Yu Guan, Daisuke Nakano, Yifan Zhang, Lei Li, Wenhua Liu, Motohiro Nishida, Takashige Kuwabara, Asahiro Morishita, Hirofumi Hitomi, Kiyoshi Mori, Masashi Mukoyama, Tsutomu Masaki, Katsuya Hirano, Akira Nishiyama
The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy. Mice were divided into 3 groups: control, doxorubicin + vehicle (15 mg/kg doxorubicin and saline) and doxorubicin + Q94 (doxorubicin at 15 mg/kg and the PAR-1 antagonist Q94 at 5 mg/kg/d) groups. Where indicated, doxorubicin was administered intravenously and PAR-1 antagonist or saline vehicle by subcutaneous osmotic mini-pump...
September 14, 2017: Journal of Pharmacological Sciences
Minlie Liang, Wenliang Zhong, Fei Miao, Hongchao Wu, Yingfeng Liu
Increased short-term blood pressure variability (BPV) is strongly correlated with target organ damage. However, the molecular mechanisms underlying abnormal BPV-induced organ damage and effective therapeutic targets are poorly understood. The purpose of this study was to investigate the effects of losartan on vasomotor function and canonical transient receptor potential (TRPC) channels in the aortas of rats with arterial pressure lability induced by sinoaortic denervation (SAD). SAD was performed in male Sprague-Dawley rats at the age of 10 weeks...
October 26, 2017: Clinical and Experimental Hypertension: CHE
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