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Zhihan Zhao, Huan Lan, Ibrahim El-Battrawy, Xin Li, Fanis Buljubasic, Katherine Sattler, Gökhan Yücel, Siegfried Lang, Malte Tiburcy, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are providing new possibilities for the biological study, cell therapies, and drug discovery. However, the ion channel expression and functions as well as regulations in hiPSC-CMs still need to be fully characterized. Methods: Cardiomyocytes were derived from hiPS cells that were generated from two healthy donors. qPCR and patch clamp techniques were used for the study. Results: In addition to the reported ion channels, INa , ICa-L , ICa-T , If , INCX , IK1 , Ito , IKr , IKs IKATP , IK-pH , ISK1-3 , and ISK4 , we detected both the expression and currents of ACh-activated (KACh) and Na+ -activated (KNa) K+ , volume-regulated and calcium-activated (Cl-Ca) Cl- , and TRPV channels...
2018: Stem Cells International
Alberto González, Claudio A Sáez, Bernardo Morales, Alejandra Moenne
The existence of functional Transient Receptor Potential (TRP) channels was analyzed in Ectocarpus siliculosus using agonists of human TRPs and specific antagonists of TRPA1, TRPC5, TRPM8 and TRPV; intracellular calcium was detected for 60 min. Increases in intracellular calcium were observed at 13, 29, 39 and 50-52 min, which appeared to be mediated by the activation of TRPM8/V1 at 13 min, TRPV1 at 29 min, TRPA1/V1 at 39 min and TRPA1/C5 at 50-52 min. In addition, intracellular calcium increases appear to be due to extracellular calcium entry, not requiring protein kinase activation...
March 2, 2018: Plant Physiology and Biochemistry: PPB
Andrew Van Cott, Markus Frericks, Charles Hastings, Naveed Honarvar, Burkhard Flick, Eric Fabian, Bennard van Ravenzwaay
Afidopyropen is a novel insecticide that acts as a TRPV channel modulator in chordotonal organs of target insects. In two carcinogenicity studies with Fischer rats, an increased incidence of uterine adenocarcinomas was observed at 1000 and 3000 ppm. This finding prompted an investigation of the mechanism of the tumor formation as well as the relevance of this mechanism to humans. The mechanistic work took parallel paths: one path investigated the pharmacokinetic properties of the test substance at the doses where the tumors were found; while the second path examined the key mechanistic events that culminated in uterine adenocarcinomas...
March 3, 2018: Regulatory Toxicology and Pharmacology: RTP
Cing-Yu Chen, Wen-Chuan Lin, Kar-Lok Wong, Ka-Shun Cheng, Yuk-Man Leung, Shu-Er Yang
Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti-cancer activities and has recently shown some success to treat glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca2+ concentration ([Ca2+ ]i ) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3-h and 18-h exposures, 10 μM gossypol caused 23 and 65% cell death, respectively; 3 μM gossypol caused no and 21% death, respectively...
March 1, 2018: Clinical and Experimental Pharmacology & Physiology
Zengqin Deng, Navid Paknejad, Grigory Maksaev, Monica Sala-Rabanal, Colin G Nichols, Richard K Hite, Peng Yuan
The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present the cryo-EM structure of Xenopus tropicalis TRPV4 at 3.8-Å resolution. The ion-conduction pore contains an intracellular gate formed by the inner helices, but lacks any extracellular gate in the selectivity filter, as observed in other TRPV channels. Anomalous X-ray diffraction analyses identify a single ion-binding site in the selectivity filter, thus explaining TRPV4 nonselectivity...
February 26, 2018: Nature Structural & Molecular Biology
Yun Zeng, Heng Han, Bing Tang, Jie Chen, Dan Mao, Min Xiong
BACKGROUND Spinal cord injury (SCI) causes a rapid loss of motor neurons, leading to weakness and paralysis. Transplantation of neural stem cells is known to restore the neuronal activity but is inefficient due to limited regenerative capability and low rate of survival. There has been an emphasis on the use of growth factors along with neural stem cells (NSCs) to enhance the neuronal recovery. Transplantation of recombinant NSCs with vascular endothelial growth factor (VEGF) might promote neuronal repair. This effect might be attributed to the reduced transient receptor potential vanilloid 1 (TRPV1) expression following transplantation...
February 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jianmin Chen, Alexander J P Hamers, Michaela Finsterbusch, Gianmichele Massimo, Maleeha Zafar, Roger Corder, Romain A Colas, Jesmond Dalli, Christoph Thiemermann, Amrita Ahluwalia
The severity of cardiac dysfunction predicts mortality in sepsis. Activation of transient receptor potential vanilloid receptor type (TRPV)-1, a predominantly neuronal nonselective cation channel, has been shown to improve outcome in sepsis and endotoxemia. However, the role of TRPV1 and the identity of its endogenous ligands in the cardiac dysfunction caused by sepsis and endotoxemia are unknown. Using TRPV1-/- and TRPV1+/+ mice, we showed that endogenous activation of cardiac TRPV1 during sepsis is key to limiting the ensuing cardiac dysfunction...
February 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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
Tobias M Backes, Oliver G Rössler, Xin Hui, Carsten Grötzinger, Peter Lipp, Gerald Thiel
Transient receptor potential vanilloid 1 (TRPV1) channels were originally described as the receptors of capsaicin, the main constituent of hot chili pepper. The biological functions of TRPV1 channels include pain sensation and inflammatory thermal hyperalgesia. Here, we show that stimulation of HEK293 cells expressing TRPV1 channels (H2C1 cells) with capsaicin or the TRPV1 ligand resiniferatoxin activated transcription mediated by the transcription factor AP-1. No cell death was occurring under these experimental conditions...
February 13, 2018: Biochemical Pharmacology
Qian Ru Gu, Yang Yang Li, Guo Rong Chen, M J Quinn
In 1937, Drs. Moritz and Oldt described arteriolar injuries in the kidneys (and other viscera) in hypertension, across the age range, in both sexes, and, in different races. This hypothesis proposes that injuries to vasomotor nerves cause the arteriolar injury in the kidney in hypertension, (as well as that in the uterus in preeclampsia). Different patterns of perivascular hyalinisation in different viscera are clues to the varying causes and consequences of arteriolar injury. In the uterus there is a symmetrical, perivascular "halo of hyalinisation" that marks the lines of extension of regenerating, injured nerves to the placental bed, whereas in the kidney there is a disordered and asymmetrical "halo of hyalinisation" where persistent, and recurrent, increases in intravascular pressures interrupt development of regenerating nerves...
February 2018: Medical Hypotheses
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
Jinfeng Jiang, Wangfang Xu, Xinggen Yu, Xiaojing Wu
To analyze the structural specificity of Shenque (CV 8) in terms of vascular biology from the three aspects of structure, tissue and molecular anatomies. On structural anatomy Shenque (CV 8) possessed defined vascular structure and was the only acupoint directly affected vascular intima. The basis of the specific therapeutic effects was owing to its relation with vessel and abundant microcirculation. Endothelial cells and microvascular endothelial cells were the tissue basis of the starting of therapeutic specificity...
December 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
M Verónica Donoso, Felipe Hernández, Tania Villalón, Claudio Acuña-Castillo, J Pablo Huidobro-Toro
Endothelial cells participate in extracellular ATP release elicited by mechanosensors. To characterize the dynamic interactions between mechanical and chemical factors that modulate ATP secretion by the endothelium, we assessed and compared the mechanisms participating in the spontaneous (basal) and mechanically stimulated secretion using primary cultures of rat mesentery endothelial cells. ATP/metabolites were determined in the cell media prior to (basal) and after cell media displacement or a picospritzer buffer puff used as mechanical stimuli...
January 19, 2018: Purinergic Signalling
Juraj Mokry, Anna Urbanova, Martin Kertys, Daniela Mokra
A group of 11 enzyme families of metalophosphohydrolases called phosphodiesterases (PDEs) is responsible for a hydrolysis of intracellular cAMP and cGMP. Xanthine derivatives (methylxanthines) inhibit PDEs without selective action on their single isoforms and lead to many pharmacological effects, e.g. bronchodilation, anti-inflammatory and immunomodulating effects, and thus they can modulate the cough reflex. Contrary, selective PDE inhibitors have been developed to inhibit PDE isoforms with different pharmacological effects based on their tissue expression...
January 11, 2018: Respiratory Physiology & Neurobiology
Taylor E T Hughes, David T Lodowski, Kevin W Huynh, Aysenur Yazici, John Del Rosario, Abhijeet Kapoor, Sandip Basak, Amrita Samanta, Xu Han, Sudha Chakrapani, Z Hong Zhou, Marta Filizola, Tibor Rohacs, Seungil Han, Vera Y Moiseenkova-Bell
The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca2+, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca2+ reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels...
January 2018: Nature Structural & Molecular Biology
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
Sandra Derouiche, Yasunori Takayama, Masataka Murakami, Makoto Tominaga
Several ion channels and transporters regulate fluid secretion in salivary and lacrimal glands. In salivary glands, the major anion channel involved in fluid secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several members of the transient receptor potential (TRP) channel superfamily regulate ANO1 activity. Here, we report a functional interaction between thermosensitive TRP vanilloid (TRPV)4 and ANO1 in acinar cells isolated from mouse salivary and lacrimal glands. TRPV4 activation induced chloride currents and shrinkage of acinar cells by increasing intracellular calcium concentrations...
January 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Nicola-Xan Hutchinson, Allen Gibbs, Amanda Tonks, Benjamin D Hope-Gill
Dry cough is a common symptom described in patients with Idiopathic Pulmonary Fibrosis (IPF) and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however evidence suggests altered cough neurophysiology and sensitisation plays a role; IPF patients have an enhanced cough reflex sensitivity to inhaled capsaicin. The Transient Receptor Potential Vanniloid-1 channel (TRPV-1) has a role in the cough reflex and airway expression is increased in patients with chronic cough. The Ankyrin-1 receptor (TRPA-1) is often co-expressed...
2017: PloS One
Lei Zhan, Jun Li
The transient receptor potential vanilloid 4 (TRPV4) is a highly Ca(2+)-permeable non-selective cation channel in TRPV family. Accumulating evidence hints that TRPV4 play a significant role in a wide diversity of pathologic changes. Fibrosis is a kind of chronic disease which was characterized by the formation of excessive accumulation of extracellular matrix (ECM) components in tissues and organs. In recent years, a growing body of studies showed that TRPV4 acted as a crucial regulator in the progression of fibrosis including myocardial fibrosis, cystic fibrosis, pulmonary fibrosis, hepatic fibrosis and pancreatic fibrosis, suggesting TRPV4 may be a potential therapeutic vehicle in fibrotic diseases...
November 7, 2017: Gene
Yanqing Wang, Brian D Burrell
Endocannabinoids, such as 2-arachidonoyl glycerol (2-AG) and anandamide, can elicit long-term depression of both excitatory and inhibitory synapses. This latter effect will result in disinhibition and would therefore be expected to produce an increase in neural circuit output. However, there have been no examples directly linking endocannabinoid-mediated disinhibition to a change in a functional neurobehavioral circuit. The present study uses the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana, to examine the functional/behavioral relevance of endocannabinoid modulation of an identified afferent synapse...
November 8, 2017: Journal of Neurophysiology
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