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Florentina Sophie Ferstl, Alice Miriam Kitay, Rebecca Marion Trattnig, Abrar Alsaihati, John Peter Geibel
Prolonged exposure to gastric acid is a leading cause of gastroesophageal reflux disease (GERD) and esophagitis. With the ever increasing number of patients showing insensitivity to proton-pump-inhibitor (PPI) therapy with recurrence of symptoms over time, alternative treatment options remain an important issue. Previous studies from our laboratory have shown that a zinc sulfate salt can inhibit HCl generation at the cellular level of the parietal cell. In this paper, we examine the difference between two hydration forms of ZnSO4 (monohydrate H2O and heptahydrate 7H2O) in their entry characteristics into the parietal cell under several physiological conditions associated with acid secretion...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
Mei Hong Zhu, Tae Sik Sung, Masaaki Kurahashi, Lauren E O'Kane, Kate O'Driscoll, Sang Don Koh, Kenton M Sanders
ICC generate electrical slow waves by coordinated openings of ANO1 channels, a Ca(2+)-activated Cl(-) (CaCC) conductance. Efflux of Cl(-) during slow waves must be significant as there is high current density during slow wave currents and slow waves are of sufficient magnitude to depolarize the syncytium of smooth muscle cells and PDGFRα(+) cells to which they are electrically coupled. We investigated how the driving force for Cl(-) current is maintained in ICC. We found robust expression of Slc12a2 (which encodes a Na(+)K(+)Cl(-) cotransporter, NKCC1) and immunohistochemical confirmation that NKCC1 is expressed in ICC...
October 13, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Ken Yamada, Ji-Hu Zhang, Xiaoling Xie, Juergen Reinhardt, Amy Qiongshu Xie, Daniel LaSala, Darcy Kohls, David Yowe, Debra Burdick, Hajime Yoshisue, Hiromichi Wakai, Isabel Schmidt, Jason Gunawan, Kayo Yasoshima, Q Kimberley Yue, Mitsunori Kato, Muneto Mogi, Neeraja Idamakanti, Natasha Kreder, Peter Drueckes, Pramod Pandey, Toshio Kawanami, Waanjeng Huang, Yukiko I Yagi, Zhan Deng, Hyi-Man Park
Protein kinases are known for their highly conserved adenosine triphosphate (ATP)-binding site, rendering the discovery of selective inhibitors a major challenge. In theory, allosteric inhibitors can achieve high selectivity by targeting less conserved regions of the kinases, often with an added benefit of retaining efficacy under high physiological ATP concentration. Although often overlooked in favor of ATP-site directed approaches, performing a screen at high ATP concentration and/or stringent hit triaging with high ATP concentration offer conceptually simple methods of identifying allosteric inhibitors...
October 7, 2016: ACS Chemical Biology
Leif Hertz, Ye Chen
Initial clearance of extracellular K(+) ([K(+)]o) following neuronal excitation occurs by astrocytic uptake, because elevated [K(+)]o activates astrocytic but not neuronal Na(+),K(+)-ATPases. Subsequently, astrocytic K(+) is re-released via Kir4.1 channels after distribution in the astrocytic functional syncytium via gap junctions. The dispersal ensures widespread release, preventing renewed [K(+)]o increase and allowing neuronal Na(+),K(+)-ATPase-mediated re-uptake. Na(+),K(+)-ATPase operation creates extracellular hypertonicity and cell shrinkage which is reversed by the astrocytic cotransporter NKCC1...
September 28, 2016: Neuroscience and Biobehavioral Reviews
Viviane Wilms, Christine Köppl, Chris Söffgen, Anna-Maria Hartmann, Hans Gerd Nothwang
In the cochlea, mammals maintain a uniquely high endolymphatic potential (EP), which is not observed in other vertebrate groups. However, a high [K(+)] is always present in the inner ear endolymph. Here, we show that Kir4.1, which is required in the mammalian stria vascularis to generate the highly positive EP, is absent in the functionally equivalent avian tegmentum vasculosum. In contrast, the molecular repertoire required for K(+) secretion, specifically NKCC1, KCNQ1, KCNE1, BSND and CLC-K, is shared between the tegmentum vasculosum, the vestibular dark cells and the marginal cells of the stria vascularis...
September 29, 2016: Scientific Reports
Ken-Ichi Nakajima, Yoshinori Marunaka
Chloride ion (Cl(-)) is one of the most abundant anions in our body. Increasing evidence suggests that Cl(-) plays fundamental roles in various cellular functions. We have previously reported that electroneutral cation-chloride cotransporters, such as Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) and K(+)-Cl(-) cotransporter 1 (KCC1), are involved in neurite outgrowth during neuronal differentiation. In the present study, we studied if there is correlation between intracellular Cl(-) concentrations ([Cl(-)]i) and the length of growing neurites...
October 14, 2016: Biochemical and Biophysical Research Communications
Julie Tomas, Céline Mulet, Azadeh Saffarian, Jean-Baptiste Cavin, Robert Ducroc, Béatrice Regnault, Chek Kun Tan, Kalina Duszka, Rémy Burcelin, Walter Wahli, Philippe J Sansonetti, Thierry Pédron
Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum-which is usually described as free of bacteria-became occupied by a dense microbiota...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Juen-Haur Hwang, Yin-Ching Chan
BACKGROUND: Although the activity of tinnitus-related ion co-transporter are known, their mRNA expressions has seldom been reported. We aimed to investigate the mRNA expressions of tinnitus-related ion co-transporter genes, and treatment effects of Spirulina. METHODS: The mRNA expressions of K(+)-Cl(-) co-transporter (KCC2) and Na-K-2Cl co-transporter 1 (NKCC1) genes in the cochlea and brain of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate...
2016: BMC Neurology
Fushun Wang, Xiaowei Wang, Lee A Shapiro, Maria L Cotrina, Weimin Liu, Ernest W Wang, Simeng Gu, Wei Wang, Xiaosheng He, Maiken Nedergaard, Jason H Huang
Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of seizures. Understanding the seizure-inducing mechanisms of TBI is of the utmost importance, because these seizures are often resistant to traditional first- and second-line anti-seizure treatments. The early post-traumatic seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these seizures...
September 1, 2016: Brain Structure & Function
Ana Cathia Magalhães, Claudio Rivera
The proliferative pool of neural progenitor cells is maintained by exquisitely controlled mechanisms for cell cycle regulation. The Na-K-Cl cotransporter (NKCC1) is important for regulating cell volume and the proliferation of different cell types in vitro. NKCC1 is expressed in ventral telencephalon of embryonic brains suggesting a potential role in neural development of this region. The ventral telencephalon is a major source for both interneuron and oligodendrocyte precursor cells. Whether NKCC1 is involved in the proliferation of these cell populations remains unknown...
2016: Frontiers in Cellular Neuroscience
Mingkun Zhang, Zhenwen Cui, Hua Cui, Yang Cao, Chunlong Zhong, Yong Wang
BACKGROUND: Astaxanthin is a carotenoid pigment that possesses potent antioxidative, anti-inflammatory, antitumor, and immunomodulatory activities. Previous studies have demonstrated that astaxanthin displays potential neuroprotective properties for the treatment of central nervous system diseases, such as ischemic brain injury and subarachnoid hemorrhage. This study explored whether astaxanthin is neuroprotective and ameliorates neurological deficits following traumatic brain injury (TBI)...
2016: BMC Neuroscience
Alvaro Cortes Cabrera, Daniel Lucena-Agell, Mariano Redondo-Horcajo, Isabel Barasoain, J Fernando Díaz, Bernhard Fasching, Paula M Petrone
Predicting the cellular response of compounds is a challenge central for the discovery of new drugs. Compound biological signatures have risen as a way of representing the perturbation produced by a compound in the cell. However, their ability to encode specific phenotypic information and generating tangible predictions remains unknown, mainly because of the inherent noise in such data sets. In this work, we statistically aggregate signal from several biological signatures to find compounds that produce a desired phenotype in the cell...
August 26, 2016: ACS Chemical Biology
Kim E Barrett, Declan F McCole
Reactive oxygen species (ROS) such as hydrogen peroxide (H2 O2 ) contribute to epithelial damage and ion transport dysfunction (key events in inflammatory diarrhea) in inflammatory bowel disease (IBD). The aim of this study was to identify if H2 O2 mediates suppression of colonic ion transport function in the murine dextran sulfate sodium (DSS) colitis model by using the H2 O2 degrading enzyme, catalase. Colitis was induced by administering DSS (4%) in drinking water for 5 days followed by 3 days on normal H2 O...
August 20, 2016: Clinical and Experimental Pharmacology & Physiology
Keisuke Kakizawa, Miho Watanabe, Hiroki Mutoh, Yuta Okawa, Miho Yamashita, Yuchio Yanagawa, Keiichi Itoi, Takafumi Suda, Yutaka Oki, Atsuo Fukuda
Corticotropin-releasing hormone (CRH), which is synthesized in the paraventricular nucleus (PVN) of the hypothalamus, plays an important role in the endocrine stress response. The excitability of CRH neurons is regulated by γ-aminobutyric acid (GABA)-containing neurons projecting to the PVN. We investigated the role of GABA in the regulation of CRH release. The release of CRH was impaired, accumulating in the cell bodies of CRH neurons in heterozygous GAD67-GFP (green fluorescent protein) knock-in mice (GAD67(+/GFP)), which exhibited decreased GABA content...
August 2016: Science Advances
Hiromitsu Miyazaki, Philine Wangemann, Daniel C Marcus
BACKGROUND: Disturbance of acid-base balance in the inner ear is known to be associated with hearing loss in a number of conditions including genetic mutations and pharmacologic interventions. Several previous physiologic and immunohistochemical observations lead to proposals of the involvement of acid-base transporters in stria vascularis. RESULTS: We directly measured acid flux in vitro from the apical side of isolated stria vascularis from adult C57Bl/6 mice with a novel constant-perfusion pH-selective self-referencing probe...
2016: BMC Physiology
Georgina MacKenzie, Kate K O'Toole, Stephen J Moss, Jamie Maguire
Glioblastoma Multiforme (GBM) is the most common form of primary brain tumor with 30-50% of patients presenting with epilepsy. These tumor-associated seizures are often resistant to traditional antiepileptic drug treatment and persist after tumor resection. This suggests that changes in the peritumoral tissue underpin epileptogenesis. It is known that glioma cells extrude pathological concentrations of glutamate which is thought to play a role in tumor progression and the development of epilepsy. Given that pathological concentrations of glutamate have been shown to dephosphorylate and downregulate the potassium chloride cotransporter KCC2, we hypothesized that glioma-induced alterations in KCC2 in the peritumoral region may play a role in tumor-associated epilepsy...
October 2016: Epilepsy Research
Ebbe Boedtkjer, Vladimir V Matchkov, Donna M B Boedtkjer, Christian Aalkjaer
Cl(-) and HCO3 (-) are the most prevalent membrane-permeable anions in the intra- and extracellular spaces of the vascular wall. Outwardly directed electrochemical gradients for Cl(-) and HCO3 (-) permit anion channel opening to depolarize vascular smooth muscle and endothelial cells. Transporters and channels for Cl(-) and HCO3 (-) also modify vascular contractility and structure independently of membrane potential. Transport of HCO3 (-) regulates intracellular pH and thereby modifies the activity of enzymes, ion channels, and receptors...
September 2016: Physiology
Loïs S Miraucourt, Jennifer Tsui, Delphine Gobert, Jean-François Desjardins, Anne Schohl, Mari Sild, Perry Spratt, Annie Castonguay, Yves De Koninck, Nicholas Marsh-Armstrong, Paul W Wiseman, Edward S Ruthazer
Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina, but the role of endocannabinoids in vision is not fully understood. Here, we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl(-) levels in RGCs, hyperpolarizing the resting membrane potential...
2016: ELife
Jiun-Jang Juo, Chao-Kai Kang, Wen-Kai Yang, Shu-Yuan Yang, Tsung-Han Lee
The present study aimed to evaluate the osmoregulatory mechanism of Daisy's medaka, O. woworae,as well as demonstrate the major factors affecting the hypo-osmoregulatory characteristics of euryhaline and stenohaline medaka. The medaka phylogenetic tree indicates that Daisy's medaka belongs to the celebensis species group. The salinity tolerance of Daisy's medaka was assessed. Our findings revealed that 20‰ (hypertonic) saltwater (SW) was lethal to Daisy's medaka. However, 62.5% of individuals survived 10‰ (isotonic) SW with pre-acclimation to 5‰ SW for one week...
August 2016: Zoological Science
Séverine Stamboulian-Platel, Arnaud Legendre, Tanguy Chabrol, Jean-Claude Platel, Fabien Pernot, Venceslas Duveau, Corinne Roucard, Michel Baudry, Antoine Depaulis
Mesiotemporal lobe Epilepsy (MTLE), the most frequent form of focal epilepsy, is often drug-resistant. Enriching the epileptic focus with GABA-releasing engineered cells has been proposed as a strategy to prevent seizures. However, ex vivo data from animal models and MTLE patients suggest that, due to changes in chloride homeostasis, GABAA receptor activation is depolarizing and partly responsible for focal interictal discharges and seizure initiation. To understand how these two contradictory aspects of GABAergic neurotransmission coexist in MTLE, we used an established mouse model of MTLE presenting hippocampal sclerosis and recurrent hippocampal paroxysmal discharges (HPDs) 30-40days after a unilateral injection of kainate in the dorsal hippocampus...
July 19, 2016: Experimental Neurology
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