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https://www.readbyqxmd.com/read/29769308/ca-2-activated-cl-currents-in-the-murine-vomeronasal-organ-enhance-neuronal-spiking-but-are-dispensable-for-male-male-aggression
#1
Jonas Münch, Gwendolyn Billig, Christian A Huebner, Trese Leinders-Zufall, Frank Zufall, Thomas J Jentsch
Ca2+-activated Cl- currents have been observed in many physiological processes, including sensory transduction in mammalian olfaction. The olfactory vomeronasal (or Jacobson's) organ (VNO) detects molecular cues originating from animals of the same species or from predators. It then triggers innate behaviors such as aggression, mating, or flight. In the VNO, Ca2+-activated Cl- channels (CaCCs) are thought to amplify the initial pheromone-evoked receptor potential by mediating a depolarizing Cl- efflux. Here, we confirmed the co-localization of the Ca2+-activated Cl- channels anoctamin 1 (Ano1, also called TMEM16A) and Ano2 (TMEM16B) in microvilli of apically and basally located vomeronasal sensory neurons (VSNs) and their absence in supporting cells of the VNO...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29758025/clca2-is-a-positive-regulator-of-store-operated-calcium-entry-and-tmem16a
#2
Aarushi Sharma, Grace Ramena, Yufang Yin, Louis Premkumar, Randolph C Elble
The Chloride Channel Accessory (CLCA) protein family was first characterized as regulators of calcium-activated chloride channel (CaCC) currents (ICaCC), but the mechanism has not been fully established. We hypothesized that CLCAs might regulate ICaCC by modulating intracellular calcium levels. In cells stably expressing human CLCA2 or vector, we found by calcium imaging that CLCA2 moderately enhanced intracellular-store release but dramatically increased store-operated entry of calcium upon cytosolic depletion...
2018: PloS One
https://www.readbyqxmd.com/read/29748496/calcium-activated-cl-channel-insights-on-the-molecular-identity-in-epithelial-tissues
#3
REVIEW
Trey S Rottgen, Andrew J Nickerson, Vazhaikkurichi M Rajendran
Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca2+ -activated Cl− secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca2+ -activated Cl− channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca2+ -sensitivity of the channel...
May 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29604966/anoctamin-9-tmem16j-is-a-cation-channel-activated-by-camp-pka-signal
#4
Hyungsup Kim, Hyesu Kim, Jesun Lee, Byeongjun Lee, Hee-Ryang Kim, Jooyoung Jung, Mi-Ock Lee, Uhtaek Oh
Anoctamins (ANOs) are multifunctional membrane proteins that consist of 10 homologs. ANO1 (TMEM16A) and ANO2 (TMEM16B) are anion channels activated by intracellular calcium that meditate numerous physiological functions. ANO6 is a scramblase that redistributes phospholipids across the cell membrane. The other homologs are not well characterized. We found ANO9/TMEM16J is a cation channel activated by a cAMP-dependent protein kinase A (PKA). Intracellular cAMP-activated robust currents in whole cells expressing ANO9, which were inhibited by a PKA blocker...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29600587/tmem16a-inhibition-impedes-capacitation-and-acquisition-of-hyperactivated-motility-in-guinea-pig-sperm
#5
Joaquín Cordero-Martínez, Tania Reyes-Miguel, Lorena Rodríguez-Páez, Leticia Garduño-Siciliano, Deneb Maldonado-García, Ana L Roa-Espitia, Enrique O Hernández-González
Ca2+ -activated Cl- channels (CaCCs) are anionic channels that regulate many important physiological functions associated with chloride and calcium flux in some somatic cells. The molecular identity of CaCCs was revealed to be TMEM16A and TMEM16B (also known as Anoctamin or ANO1 and ANO2, respectively) in all eukaryotes. A recent study suggests the presence of TMEM16A in human sperm and a relationship with the rhZP-induced acrosome reaction. However, to the best of our knowledge, little is known about the role of TMEM16A in other spermatic processes such as capacitation or motility...
March 30, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29561662/dextran-sulfate-sodium-dss-induced-chronic-colitis-attenuates-ca-2-activated-cl-secretion-in-murine-colon-by-down-regulating-tmem16a
#6
Trey S Rottgen, Andrew J Nickerson, Emily A Minor, Amanda B Stewart, Abby D Harold, Vazhaikkurichi M Rajendran
Attenuated Ca2+ -activated Cl- secretion has previously been observed in the model of dextran-sulfate-sodium (DSS)-induced colitis. Prior studies have implicated dysfunctional muscarinic signaling from basolateral membranes as the potential perpetrator leading to decreased Ca2+ -activated Cl- secretion. However, in our chronic model of DSS-colitis, Chrm3 transcript (1.028 {plus minus} 0.12 vs. 1.029 {plus minus} 0.27, p > 0.05) and CHRM3 protein expression (1.021 {plus minus} .24 vs. .928 {plus minus} .09, p > 0...
March 21, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29492471/ion-channel-gene-expressions-in-infertile-men-a-case-control-study
#7
Serkan Carkci, Ebru Onalan Etem, Seda Ozaydin, Ahmet Karakeci, Ahmet Tektemur, Tunc Ozan, Irfan Orhan
Background: Infertility is described as not receiving pregnancy despite unprotected and regular sexual intercourse in a 1 yr period. It is detected by 15% of the couples. Male and female factor in the etiology may be detected in similar rates. Objective: The present study aims to investigate ion channel gene expression in semen samples of infertile male compared with fertile men. Materials and Methods: A total of 150 men who applied to the urology clinic due to infertility were divided into five equal groups: asthenozoospermia, oligozoospermia, oligoasthenoteratozoospermia, teratozoospermia, and normozoospermia (control)...
December 2017: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/29486056/defining-the-ionic-mechanisms-of-optogenetic-control-of-vascular-tone-by-channelrhodopsin-2
#8
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
https://www.readbyqxmd.com/read/29478917/the-sixth-transmembrane-segment-is-a-major-gating-component-of-the-tmem16a-calcium-activated-chloride-channel
#9
Christian J Peters, John M Gilchrist, Jason Tien, Neville P Bethel, Lijun Qi, Tingxu Chen, Lynn Wang, Yuh Nung Jan, Michael Grabe, Lily Y Jan
Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating...
March 7, 2018: Neuron
https://www.readbyqxmd.com/read/29472628/ultrastructural-and-immunohistochemical-features-of-telocytes-in-placental-villi-in-preeclampsia
#10
Natalia V Nizyaeva, Tatiana V Sukhacheva, Roman A Serov, Galina V Kulikova, Marina N Nagovitsyna, Natalia E Kan, Victor L Tyutyunnik, Stanislav V Pavlovich, Rimma A Poltavtseva, Ekaterina L Yarotskaya, Aleksandr I Shchegolev, Gennadiy T Sukhikh
A new cell type, interstitial Cajal-like cell (ICLC), was recently described in different organs. The name was recently changed to telocytes (TCs), and their typical thin, long processes have been named telopodes (Tp). TCs regulate the contractile activity of smooth muscle cells and play a role in regulating vessel contractions. Although the placenta is not an innervated organ, we believe that TCs are present in the placenta. We studied placenta samples from physiological pregnancies and in different variants of preeclampsia (PE)...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29438598/variable-contribution-of-tmem16a-to-tone-in-murine-arterial-vasculature
#11
Anders Bisgaard Jensen, Henrik Black Joergensen, Vibeke Secher Dam, Dmitrii Kamaev, Donna Boedtkjer, Ernst-Martin Füchtbauer, Christian Aalkjaer, Vladimir V Matchkov
TMEM16A is essential for Ca2+ -activated Cl- conductance in vascular smooth muscle. The importance of TMEM16A for agonist-induced vascular constriction and blood pressure control is, however, under debate. Previous studies suggested that TMEM16A might have a complex cellular function beyond being essential for the Ca2+ -activated Cl- conductance, for example modulation of Ca2+ channel expression. Mice with constitutive, smooth muscle-specific expression of siRNA directed against Tmem16a (transgenic mice, TG) were generated...
February 13, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29434696/tmem16a-regulates-portal-vein-smooth-muscle-cell-proliferation-in-portal-hypertension
#12
Xi Zeng, Ping Huang, Mingkai Chen, Shiqian Liu, Nannan Wu, Fang Wang, Jing Zhang
The aim of the present study was to elucidate the effect of transmembrane protein 16A (TMEM16A) on portal vein smooth muscle cell (PVSMC) proliferation associated with portal vein remodeling in portal hypertension (PHT). Sprague-Dawley rats were subjected to bile duct ligation to establish a rat model of liver cirrhosis and PHT. Sham-operated animals served as controls. At 8 weeks after bile duct ligation, the extent of liver fibrosis and the portal vein wall thickness were assessed using hematoxylin-eosin staining...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29360145/bile-acids-stimulate-cholangiocyte-fluid-secretion-by-activation-of-membranetmem16a-cl-channels
#13
Qin Li, Amal Dutta, Charles Kresge, Abhijit Bugde, Andrew P Feranchak
Bile acids stimulate a bicarbonate-rich choleresis in part through effects on cholangiocytes. As Cl- channels in the apical membrane of cholangiocytes provide the driving force for secretion and TMEM16A has been identified as the Ca2+ -activated Cl- channel in the apical membrane of cholangiocytes (1), the aim of the present study was to determine if TMEM16A is the target of bile acid-stimulated Cl- secretion and to identify the regulatory pathway involved. In these studies of mouse, rat, and human biliary epithelium exposure to Ursodeoxycholic acid (UDCA) or Tauroursodeoxycholic acid (TUDCA) rapidly increased the rate of exocytosis, ATP release, [Ca2+ ]i , membrane Cl- permeability, and transepithelial secretion...
January 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29331508/compartmentalized-crosstalk-of-cftr-and-tmem16a-ano1-through-epac1-and-adcy1
#14
Joana Lérias, Madalena Pinto, Roberta Benedetto, Rainer Schreiber, Margarida Amaral, Massimo Aureli, Karl Kunzelmann
Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca2+ - and cAMP-dependent signaling...
April 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29277655/phosphatidylinositol-4-5-bisphosphate-cholesterol-and-fatty-acids-modulate-the-calcium-activated-chloride-channel-tmem16a-ano1
#15
José J De Jesús-Pérez, Silvia Cruz-Rangel, Ángeles E Espino-Saldaña, Ataúlfo Martínez-Torres, Zhiqiang Qu, H Criss Hartzell, Nancy E Corral-Fernandez, Patricia Pérez-Cornejo, Jorge Arreola
The TMEM16A-mediated Ca2+ -activated Cl- current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca2+ ...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29236691/activation-mechanism-of-the-calcium-activated-chloride-channel-tmem16a-revealed-by-cryo-em
#16
Cristina Paulino, Valeria Kalienkova, Andy K M Lam, Yvonne Neldner, Raimund Dutzler
The calcium-activated chloride channel TMEM16A is a ligand-gated anion channel that opens in response to an increase in intracellular Ca2+ concentration. The protein is broadly expressed and contributes to diverse physiological processes, including transepithelial chloride transport and the control of electrical signalling in smooth muscles and certain neurons. As a member of the TMEM16 (or anoctamin) family of membrane proteins, TMEM16A is closely related to paralogues that function as scramblases, which facilitate the bidirectional movement of lipids across membranes...
December 21, 2017: Nature
https://www.readbyqxmd.com/read/29236684/cryo-em-structures-of-the-tmem16a-calcium-activated-chloride-channel
#17
Shangyu Dang, Shengjie Feng, Jason Tien, Christian J Peters, David Bulkley, Marco Lolicato, Jianhua Zhao, Kathrin Zuberbühler, Wenlei Ye, Lijun Qi, Tingxu Chen, Charles S Craik, Yuh Nung Jan, Daniel L Minor, Yifan Cheng, Lily Yeh Jan
Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy...
December 21, 2017: Nature
https://www.readbyqxmd.com/read/29229864/cytoplasmic-cl-couples-membrane-remodeling-to-epithelial-morphogenesis
#18
Mu He, Wenlei Ye, Won-Jing Wang, Eirish S Sison, Yuh Nung Jan, Lily Yeh Jan
Chloride is the major free anion in the extracellular space (>100 mM) and within the cytoplasm in eukaryotes (10 ∼ 20 mM). Cytoplasmic Cl- level is dynamically regulated by Cl- channels and transporters. It is well established that movement of Cl- across the cell membrane is coupled with cell excitability through changes in membrane potential and with water secretion. However, whether cytoplasmic Cl- plays additional roles in animal development and tissue homeostasis is unknown. Here we use genetics, cell biological and pharmacological tools to demonstrate that TMEM16A, an evolutionarily conserved calcium-activated chloride channel (CaCC), regulates cytoplasmic Cl- homeostasis and promotes plasma membrane remodeling required for mammalian epithelial morphogenesis...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29187602/tmem16a-and-tmem16b-channel-proteins-generate-ca-2-activated-cl-current-and-regulate-melatonin-secretion-in-rat-pineal-glands
#19
Hisao Yamamura, Kaori Nishimura, Yumiko Hagihara, Yoshiaki Suzuki, Yuji Imaizumi
Pinealocytes regulate circadian rhythm by synthesizing and secreting melatonin. These cells generate action potentials; however, the contribution of specific ion channels to melatonin secretion from pinealocytes remains unclear. In this study, the involvement and molecular identity of Ca2+ -activated Cl- (ClCa ) channels in the regulation of melatonin secretion were examined in rat pineal glands. Treatment with the ClCa channel blockers, niflumic acid or T16Ainh -A01, significantly reduced melatonin secretion in pineal glands...
January 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29160910/epithelial-disruptions-but-not-immune-cell-invasion-induced-secretory-dysfunction-following-innate-immune-activation-in-a-novel-model-of-acute-salivary-gland-injury
#20
Abeer Shaalan, Guy Carpenter, Gordon Proctor
BACKGROUND: Salivary gland (SG) injurious agents are all translated into loss of salivation (xerostomia). An association has been established between activation of innate immunity and SG injury and dysfunction. However, it remains unclear how the secretory epithelia respond by halting saliva production. METHODS: C57BL/6 submandibular glands (SMGs) were acutely challenged using a single dose of the innate immune stimulant: polyinosinic-polycytidylic acid (poly (I:C))...
February 2018: Journal of Oral Pathology & Medicine
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