DOCSLIB.ORG

Effects of Aquaporin 4 and Inward Rectifier

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effects of Aquaporin 4 and Inward Rectifier 9-Experimental Surgery Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats1 Ye LiI, Haifeng HuII, Jingchen LiuIII, Qingsan ZhuIV, Rui GuV IAssociate Professor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Conception, design, intellectual and scientific content of the study; acquisition of data; manuscript writing; critical revision. IIAttending Doctor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Acquisition of data, manuscript writing. IIIProfessor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Scientific content of the study, acquisition of data, manuscript writing. IVProfessor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Acquisition of data. VProfessor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Intellectual, scientific, conception and design of the study; critical revision. Abstract Purpose: To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Methods: Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP- treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet–dry weights method was applied to measure the water content of the spinal cord. Results: The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. Conclusion: Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues. Key words: Methylprednisolone. Spinal Cord Injuries. Aquaporin 4. Potassium Channels. Rats. DOI: http://dx.doi.org/10.1590/s0102-865020180020000009 Acta Cir Bras. 2018;33(2):175-184 175 Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal Acta Cir Bras. 2018;33(2):175-184 edema after methylprednisolone treatment to suppress acute spinal cord injury in rats Li Y et al. ■ Introduction with the degree of brain edema, and Kir4.1 was transported by AQP4-coupled mediating Acute spinal cord injury (ASCI) is a water6. However, the combined effects of Kir4.1 trauma-induced spinal cord disorder; current and AQP4 on medullospinal edema secondary research mainly focuses on preventing to spinal cord injury have not been reported. secondary spinal cord injuries, promoting Methylprednisolone (MP) is the most regeneration of the spinal cord, and replacing widely studied and recognized glucocorticoid the injured medullospinal tissues1. Spinal cord drug for the treatment of spinal cord injury; it injuries are usually divided into primary and is also the only Food and Drug Administration- secondary injuries; the former refers to direct approved drug for the clinical treatment of and irreversible tissue injury to the spinal cord, ASCI in the United States7. In response to spinal which may be followed by secondary spinal cord cord injury, MP mediates antioxidative, anti- injury. Injury results in the release of a large inflammatory, and immunosuppressive effects; number of self-destructive mediators that lead stabilizes cell and lysosomal membranes; to hypoxia–ischemia, edema, degeneration, reduces medullospinal tissue deficiency at and necrosis of the spinal cord2. Therefore, the injured site; improves blood flow to the protecting the uninjured portions of the spinal injured spinal cord segment; reduces edema; cord and suppressing medullospinal edema are increases the activity of Na+/K+-dependent the key early treatments for ASCI. However, the ATP enzyme; increases the resting potentials mechanisms of ASCI-induced medullospinal and excitabilities of spinal cord motor fibers; edema are still unclear. Aquaporins (AQPs) and promotes the generation and conduction are closely related to tissue edema and AQP4 of spinal cord impulses8. In this study, we is the most studied isoform in the central observed the impact of MP on medullospinal nervous system, as it is widely distributed in edema in rats with ASCI, and investigated the the brain and spinal cord; it is closely related Kir4.1- and AQP4-related mechanisms of MP- to trauma-induced brain and medullospinal mediated suppression of medullospinal edema edema. Oklinski et al.3 found that AQP4 is in rats with ASCI. mainly expressed in the astrocytes of the rat spinal cord, as well as in the gray matter and ■ Methods white matter of the spinal cord; it is most highly expressed on the membranes of perivascular This study was carried out in strict astrocytes in the gray matter. AQP4 participates accordance with the recommendations in in the transportation of water molecules in the the Guide for the Care and Use of Laboratory brain, as well as the regulation of electrolytes Animals of the National Institutes of Health. and osmotic pressure, in the physiological state; The animal use protocol has been reviewed under pathological conditions, it is involved and approved by the Institutional Animal Care in tissue edema caused by bodily injury4. and Use Committee (IACUC) of Jilin University. Overexpression of AQP4 in the gray matter Healthy, male Sprague Dawley (SD) of the spinal cord indicates that AQP4 might rats (250–300 g) were provided by the play an important role in regulating the water Experimental Animal Center of Jilin University; balance of the spinal cord. Inward rectifier rat breeding and experimental manipulations potassium channel 4.1 (Kir4.1) participates in were performed in accordance with the not only the formation of action potentials, but management and protection requirements also water transportation, in brain tissues5. The for experimental animals. The rats were expression of Kir4.1 in rats with focal cerebral bred by special individuals, and maintained ischemia/reperfusion positively correlated with 6 rats to a cage, with free access to 176 Acta Cir Bras. 2018;33(2):175-184 Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats Li Y et al. food and drinking water on a 12-h light/dark the sham-group rats were incised to expose the cycle, at 22°C±3°C. We utilized MP (Sigma- dural sac without the use of a spinal cord clip to Aldrich, USA); a BCA protein concentration damage the spinal cord. After the surgery, the detection kit, polyvinylidene fluoride (PVDF) rats from each group were fed separately, and membranes, 100 ug of protein were loaded per assisted with urination and defecation in the lane, and protein molecular weight standards early post-operative stages. The rats in the MP (Invitrogen, USA); anti-AQP4 (PA1220, BOSTER, group were slowly injected with 30 mg/kg MP China) and anti--Kir4.1 (A02619, BOSTER, solution via the tail vein within 1 h of the ASCI China) monoclonal antibodies, anti-β-actin surgery; the total, 23-h dose was calculated primary antibody (1:1000 dilution, WL0002, according to 5.4 mg/kg/h, and injected once wanleibio, China), and horseradish peroxidase every 8 h; the injection time points were post- conjugated anti-rabbit secondary antibody (0.2 operative days 3 and 7. µg/ml, WLA023, wanleibio, China), a vertical electrophoresis and membrane-transferring Tarlov scoring system (Hoefer, USA); and a quantitative A modified Tarlov scoring method was polymerase chain reaction (PCR) instrument applied to score the motor functions of the (Exicycler 96, BIONEER). rats in each group at 8 h, 24 h, 3 d, and 7 d Experimental grouping and the establishment post-surgery, to determine the success of the of an ASCI animal model modeling. The scoring criteria were as follows: 0, complete paralysis without reaction to SD rats were randomly divided into lower limb acupuncture; 1, complete paralysis control, sham, ASCI, and MP groups, with with reaction to lower limb acupuncture, but 10 rats in each group. After weighing them, inability to move limbs; 2, limb movement, but we anesthetized the rats by intraperitoneal inability to stand or stand stably (<5 s); 3, ability injection of 10% chloral hydrate (3 mg/kg); to stand, but not walk; 4, ability to walk a few we then fixed them in the prone position on unstable steps; 5, ability to walk slowly but the operating table, removed their back fur, inflexibly with some defects; 6, ability to walk and disinfected their skin. The T6 spinous normally. The rats with motor nerve function process was set as the center, and a single, scores from 0 to 2 were deemed to successfully approximately 5-cm incision was made along model ASCI, and were selected for subsequent the middle of the back to expose the T5 to T7 experiments. spinous processes and lamina; the T6 spinous Water content detection in medullospinal process and lamina were removed to reveal tissues approximately 0.5 cm of dural sac. The width of a spinal cord clip was adjusted to 1 mm and its Five rats in each group were randomly 2 blades were placed along the bilateral sides selected, and anesthetized with 10% chloral of the dural sac of the rats in the ASCI and MP hydrate (3 mg/kg); the incision of the original groups, then quickly adjusted to 2 mm and approach was reopened, the paraspinal clipped to the spinal cord for approximately muscles were peeled to expose the T5 to T7 1 min; spasm and swing of the rats’ lower lamina, then the T5 to T7 spinal cord segments limbs and tail indicated that the spinal cord were removed.
Load more

Recommended publications
  • Combined Pharmacological Administration of AQP1 Ion Channel
    www.nature.com/scientificreports OPEN Combined pharmacological administration of AQP1 ion channel blocker AqB011 and water channel Received: 15 November 2018 Accepted: 13 August 2019 blocker Bacopaside II amplifes Published: xx xx xxxx inhibition of colon cancer cell migration Michael L. De Ieso 1, Jinxin V. Pei 1, Saeed Nourmohammadi1, Eric Smith 1,2, Pak Hin Chow1, Mohamad Kourghi1, Jennifer E. Hardingham 1,2 & Andrea J. Yool 1 Aquaporin-1 (AQP1) has been proposed as a dual water and cation channel that when upregulated in cancers enhances cell migration rates; however, the mechanism remains unknown. Previous work identifed AqB011 as an inhibitor of the gated human AQP1 cation conductance, and bacopaside II as a blocker of AQP1 water pores. In two colorectal adenocarcinoma cell lines, high levels of AQP1 transcript were confrmed in HT29, and low levels in SW480 cells, by quantitative PCR (polymerase chain reaction). Comparable diferences in membrane AQP1 protein levels were demonstrated by immunofuorescence imaging. Migration rates were quantifed using circular wound closure assays and live-cell tracking. AqB011 and bacopaside II, applied in combination, produced greater inhibitory efects on cell migration than did either agent alone. The high efcacy of AqB011 alone and in combination with bacopaside II in slowing HT29 cell motility correlated with abundant membrane localization of AQP1 protein. In SW480, neither agent alone was efective in blocking cell motility; however, combined application did cause inhibition of motility, consistent with low levels of membrane AQP1 expression. Bacopaside alone or combined with AqB011 also signifcantly impaired lamellipodial formation in both cell lines. Knockdown of AQP1 with siRNA (confrmed by quantitative PCR) reduced the efectiveness of the combined inhibitors, confrming AQP1 as a target of action.
    [Show full text]
  • Ubiquitination of Aquaporin-2 in the Kidney
    Electrolytes & Blood Pressure 7:1-4, 2009 1 Review article 1) Ubiquitination of Aquaporin-2 in the Kidney Yu-Jung Lee, M.D. and Tae-Hwan Kwon, M.D. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attach - ment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation. Key Words : kidney tubules, collecting; ubiquitination; vasopressins; aquaporin 2 The kidneys are responsible for the regulation of body This process produces concentrated urine and is essential water and electrolyte metabolism. Thus, understanding of for regulation of body water metabolism 6) . In contrast to the underlying mechanisms for renal water transport is the well-established signaling pathways for the vaso- critical. Water permeability along the nephron has already pressin-regulated AQP2 trafficking and up-regulation of been well characterized in the mammalian kidney 1) . AQP2 expression, the underlying mechanisms for AQP2 Approximately, 180 L/day of glomerular filtrate is gen- endocytosis and intracellular degradation of AQP2 protein erated in an adult human, more than 80-90% of the glomer- are unclear. So far, two hormones (prostaglandin E2 and ular filtrate is constitutively reabsorbed by the highly water dopamine) cause AQP2 internalization independent of permeable proximal tubules and descending thin limbs of S256 dephosphorylation 7, 8) .
    [Show full text]
  • Microarray Analysis Reveals the Inhibition of Intestinal Expression Of
    www.nature.com/scientificreports OPEN Microarray analysis reveals the inhibition of intestinal expression of nutrient transporters in piglets infected with porcine epidemic diarrhea virus Junmei Zhang1,3, Di Zhao1,3, Dan Yi1,3, Mengjun Wu1, Hongbo Chen1, Tao Wu1, Jia Zhou1, Peng Li1, Yongqing Hou1* & Guoyao Wu2 Porcine epidemic diarrhea virus (PEDV) infection can induce intestinal dysfunction, resulting in severe diarrhea and even death, but the mode of action underlying these viral efects remains unclear. This study determined the efects of PEDV infection on intestinal absorption and the expression of genes for nutrient transporters via biochemical tests and microarray analysis. Sixteen 7-day-old healthy piglets fed a milk replacer were randomly allocated to one of two groups. After 5-day adaption, piglets (n = 8/ group) were orally administrated with either sterile saline or PEDV (the strain from Yunnan province) 4.5 at 10 TCID50 (50% tissue culture infectious dose) per pig. All pigs were orally infused D-xylose (0.1 g/ kg BW) on day 5 post PEDV or saline administration. One hour later, jugular vein blood samples as well as intestinal samples were collected for further analysis. In comparison with the control group, PEDV infection increased diarrhea incidence, blood diamine oxidase activity, and iFABP level, while reducing growth and plasma D-xylose concentration in piglets. Moreover, PEDV infection altered plasma and jejunal amino acid profles, and decreased the expression of aquaporins and amino acid transporters (L-type amino acid
    [Show full text]
  • Modulation of Voltage-Gated Potassium Channels by Phosphatidylinositol-4,5-Bisphosphate Marina Kasimova
    Modulation of voltage-gated potassium channels by phosphatidylinositol-4,5-bisphosphate Marina Kasimova To cite this version: Marina Kasimova. Modulation of voltage-gated potassium channels by phosphatidylinositol-4,5- bisphosphate. Other. Université de Lorraine, 2014. English. NNT : 2014LORR0204. tel-01751176 HAL Id: tel-01751176 https://hal.univ-lorraine.fr/tel-01751176 Submitted on 29 Mar 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. AVERTISSEMENT Ce document est le fruit d'un long travail approuvé par le jury de soutenance et mis à disposition de l'ensemble de la communauté universitaire élargie. Il est soumis à la propriété intellectuelle de l'auteur. Ceci implique une obligation de citation et de référencement lors de l’utilisation de ce document. D'autre part, toute contrefaçon, plagiat, reproduction illicite encourt une poursuite pénale. Contact : [email protected] LIENS Code de la Propriété Intellectuelle. articles L 122. 4 Code de la Propriété Intellectuelle. articles L 335.2- L 335.10 http://www.cfcopies.com/V2/leg/leg_droi.php
    [Show full text]
  • I REGENERATIVE MEDICINE APPROACHES to SPINAL CORD
    REGENERATIVE MEDICINE APPROACHES TO SPINAL CORD INJURY A Dissertation Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Ashley Elizabeth Mohrman March 2017 i ABSTRACT Hundreds of thousands of people suffer from spinal cord injuries in the U.S.A. alone, with very few patients ever experiencing complete recovery. Complexity of the tissue and inflammatory response contribute to this lack of recovery, as the proper function of the central nervous system relies on its highly specific structural and spatial organization. The overall goal of this dissertation project is to study the central nervous system in the healthy and injured state so as to devise appropriate strategies to recover tissue homeostasis, and ultimately function, from an injured state. A specific spinal cord injury model, syringomyelia, was studied; this condition presents as a fluid filled cyst within the spinal cord. Molecular evaluation at three and six weeks post-injury revealed a large inflammatory response including leukocyte invasion, losses in neuronal transmission and signaling, and upregulation in important osmoregulators. These included osmotic stress regulating metabolites betaine and taurine, as well as the betaine/GABA transporter (BGT-1), potassium chloride transporter (KCC4), and water transporter aquaporin 1 (AQP1). To study cellular behavior in native tissue, adult neural stem cells from the subventricular niche were differentiated in vitro. These cells were tested under various culture conditions for cell phenotype preferences. A mostly pure (>80%) population of neural stem cells could be specified using soft, hydrogel substrates with a laminin coating and interferon-γ supplementation.
    [Show full text]
  • An Aquaporin-4/Transient Receptor Potential Vanilloid 4 (AQP4/TRPV4) Complex Is Essential for Cell-Volume Control in Astrocytes
    An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes Valentina Benfenatia,1, Marco Caprinib,1, Melania Doviziob, Maria N. Mylonakouc, Stefano Ferronib, Ole P. Ottersenc, and Mahmood Amiry-Moghaddamc,2 aInstitute for Nanostructured Materials, Consiglio Nazionale delle Ricerche, 40129 Bologna, Italy; bDepartment of Human and General Physiology, University of Bologna, 40127 Bologna, Italy; and cCenter for Molecular Biology and Neuroscience and Department of Anatomy, University of Oslo, 0317 Oslo, Norway Edited* by Peter Agre, Johns Hopkins Malaria Research Institute, Baltimore, MD, and approved December 27, 2010 (received for review September 1, 2010) Regulatory volume decrease (RVD) is a key mechanism for volume channels (VRAC). Osmolyte efflux through VRAC is thought to control that serves to prevent detrimental swelling in response to provide the driving force for water exit (6, 7). The factors that hypo-osmotic stress. The molecular basis of RVD is not understood. initiate RVD have received comparatively little attention. Here Here we show that a complex containing aquaporin-4 (AQP4) and we test our hypothesis that activation of astroglial RVD depends transient receptor potential vanilloid 4 (TRPV4) is essential for RVD on a molecular interaction between AQP4 and TRPV4. fi in astrocytes. Astrocytes from AQP4-KO mice and astrocytes treated Our hypothesis rests on our recent nding that TRPV4 is with TRPV4 siRNA fail to respond to hypotonic stress by increased strongly expressed in astrocytic endfeet membranes abutting the – intracellular Ca2+ and RVD. Coimmunoprecipitation and immunohis- pia (including the extension of the pia that lines the Virchow tochemistry analyses show that AQP4 and TRPV4 interact and coloc- Robin spaces) and in endfeet underlying ependyma of the ven- alize.
    [Show full text]
  • Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins
    Lens Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins Sindhu Kumari,1 Junyuan Gao,1 Richard T. Mathias,1,2 Xiurong Sun,1 Amizhdini Eswaramoorthy,1 Nicholas Browne,1 Nigel Zhang,1 and Kulandaiappan Varadaraj1,2 1Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, United States 2SUNY Eye Institute, Syracuse, New York, United States Correspondence: Kulandaiappan PURPOSE. The objective of this study was to understand the molecular and physiologic Varadaraj, Department of Physiology mechanisms behind the lens cataract differences in Aquaporin 0-knockout-Heterozygous and Biophysics, BST-6, Room # 165A, (AQP0-Htz) mice developed in C57 and FVB (lacks beaded filaments [BFs]) strains. School of Medicine, Stony Brook University, NY 11794-8661, USA; METHODS. Lens transparency was studied using dark field light microscopy. Water permeability kulandaiappan.varadaraj@ (Pf) was measured in fiber cell membrane vesicles. Western blotting/immunostaining was stonybrook.edu. performed to verify expression of BF proteins and connexins. Microelectrode-based intact Submitted: May 2, 2017 lens intracellular impedance was measured to determine gap junction (GJ) coupling Accepted: October 23, 2017 resistance. Lens intracellular hydrostatic pressure (HP) was determined using a microelec- trode/manometer system. Citation: Kumari S, Gao J, Mathias RT, et al. Aquaporin 0 modulates lens gap RESULTS. Lens opacity and spherical aberration were more distinct in AQP0-Htz lenses from junctions in the presence of lens- FVB than C57 strains. In either background, compared to wild type (WT), AQP0-Htz lenses specific beaded filament proteins. showed decreased Pf (approximately 50%), which was restored by transgenic expression of Invest Ophthalmol Vis Sci.
    [Show full text]
  • Receptor-Mediated Endocytosis and Endosomal Acidification Is Impaired
    Receptor-mediated endocytosis and endosomal acidification is impaired in proximal tubule epithelial cells of Dent disease patients Caroline M. Gorvina, Martijn J. Wilmerb, Sian E. Pireta, Brian Hardinga, Lambertus P. van den Heuvelc,d, Oliver Wronge, Parmjit S. Jatf, Jonathan D. Lippiatg, Elena N. Levtchenkoc,d, and Rajesh V. Thakkera,1 aAcademic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, United Kingdom; bDepartment of Pharmacology and Toxicology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Sciences, 6500 HB, Nijmegen, The Netherlands; cLaboratory of Genetic, Endocrine and Metabolic Disorders, Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands; dDepartment of Development and Regeneration, Catholic University, 3000 Leuven, Belgium; eDepartment of Medicine, University College London, London WC1E 6AU, United Kingdom; fDepartment of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom; and gInstitute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom Edited by Andrew Rees, Medical University of Vienna, Vienna, Austria, and accepted by the Editorial Board March 12, 2013 (received for review January 31, 2013) Receptor-mediated endocytosis, involving megalin and cubilin, through this pathway requires endosomal luminal acidification that mediates renal proximal-tubular reabsorption and is decreased in facilitates ligand-receptor dissociation, ligand processing, receptor Dent disease because of mutations of the chloride/proton antiporter, recycling or degradation, vesicular trafficking, and fusion to late chloride channel-5 (CLC-5), resulting in low-molecular-weight pro- endosomes and lysosomes (5).
    [Show full text]
  • Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity
    Neuron Review Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity James S. Trimmer1,2,* 1Department of Neurobiology, Physiology, and Behavior 2Department of Physiology and Membrane Biology University of California, Davis, Davis, CA 95616, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.neuron.2014.12.042 Potassium channels (KChs) are the most diverse ion channels, in part due to extensive combinatorial assem- bly of a large number of principal and auxiliary subunits into an assortment of KCh complexes. Their structural and functional diversity allows KChs to play diverse roles in neuronal function. Localization of KChs within specialized neuronal compartments defines their physiological role and also fundamentally impacts their activity, due to localized exposure to diverse cellular determinants of channel function. Recent studies in mammalian brain reveal an exquisite refinement of KCh subcellular localization. This includes axonal KChs at the initial segment, and near/within nodes of Ranvier and presynaptic terminals, dendritic KChs found at sites reflecting specific synaptic input, and KChs defining novel neuronal compartments. Painting the remarkable diversity of KChs onto the complex architecture of mammalian neurons creates an elegant pic- ture of electrical signal processing underlying the sophisticated function of individual neuronal compart- ments, and ultimately neurotransmission and behavior. Introduction genes are expressed in distinct cellular expression patterns Mammalian brain neurons are distinguished from other cells by throughout the brain, such that particular neurons express spe- extreme molecular and structural complexity that is intimately cific combinations of KCh a and auxiliary subunits. However, the linked to the array of intra- and intercellular signaling events proteomic complexity of KChs is much greater, as KChs exist as that underlie brain function.
    [Show full text]
  • The Relevance of Aquaporins for the Physiology, Pathology, and Aging of the Female Reproductive System in Mammals
    cells Review The Relevance of Aquaporins for the Physiology, Pathology, and Aging of the Female Reproductive System in Mammals Paweł Kordowitzki 1,2 , Wiesława Kranc 3, Rut Bryl 3, Bartosz Kempisty 3,4,5, Agnieszka Skowronska 6 and Mariusz T. Skowronski 1,* 1 Department of Basic and Preclinical Sciences, Institute for Veterinary Medicine, Nicolaus Copernicus University, 87-100 Torun, Poland; [email protected] 2 Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, 10-243 Olsztyn, Poland 3 Department of Anatomy, Poznan University of Medical Sciences, 60-781 Poznan, Poland; [email protected] (W.K.); [email protected] (R.B.); [email protected] (B.K.) 4 Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland 5 Department of Veterinary Surgery, Institute for Veterinary Medicine, Nicolaus Copernicus University, 87-100 Torun, Poland 6 Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Warszawska Street 30, 10-082 Olsztyn, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-56-611-2231 Received: 27 October 2020; Accepted: 29 November 2020; Published: 1 December 2020 Abstract: Aquaporins constitute a group of water channel proteins located in numerous cell types. These are pore-forming transmembrane proteins, which mediate the specific passage of water molecules through membranes. It is well-known that water homeostasis plays a crucial role in different reproductive processes, e.g., oocyte transport, hormonal secretion, completion of successful fertilization, blastocyst formation, pregnancy, and birth. Further, aquaporins are involved in the process of spermatogenesis, and they have been reported to be involved during the storage of spermatozoa.
    [Show full text]
  • Direct Immunogold Labeling of Aquaporin-4 in Square Arrays of Astrocyte and Ependymocyte Plasma Membranes in Rat Brain and Spinal Cord
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 11981–11986, September 1998 Neurobiology Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord i JOHN E. RASH*†‡§,THOMAS YASUMURA*, C. SUE HUDSON*, PETER AGRE¶, AND SØREN NIELSEN *Department of Anatomy and Neurobiology, †Program in Molecular, Cellular, and Integrative Neurosciences, and ‡Program in Cell and Molecular Biology, Colorado State University, Fort Collins, CO 80523; ¶Departments of Biological Chemistry and Medicine, Johns Hopkins University School of Medicine; and iDepartment of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark Communicated by Thomas S. Reese, National Institutes of Health, Bethesda, MD, August 13, 1998 (received for review March 1, 1998) ABSTRACT Aquaporin (AQP) water channels are abun- the glia limitans and that surround capillaries (3). AQP4 is dant in the brain and spinal cord, where AQP1 and AQP4 are especially abundant in astrocytes and ependymocytes in os- believed to play major roles in water metabolism and osmo- mosensory areas, including the supraoptic nucleus and sub- regulation. Immunocytochemical analysis of the brain re- fornical organ (3). These sites suggest a role for AQP4 in water cently revealed that AQP4 has a highly polarized distribution, transport between the brain parenchyma, cerebrospinal fluid, with marked expression in astrocyte end-feet that surround and blood, as well as a role in osmoregulation. capillaries and form the glia limitans; however, the structural Naturally occurring membranes enriched in AQP1 contain organization of AQP4 has remained unknown. In freeze- intramembrane particles (IMPs). Nevertheless, membrane re- fracture replicas, astrocyte end-feet contain abundant square constitution of AQP1 at high concentration yielded highly arrays of intramembrane particles that parallel the distribu- ordered two-dimensional crystalline lattices of AQP1, with a tion of AQP4.
    [Show full text]
  • Characterization of Membrane Proteins: from a Gated Plant Aquaporin to Animal Ion Channel Receptors
    Characterization of Membrane Proteins: From a gated plant aquaporin to animal ion channel receptors Survery, Sabeen 2015 Link to publication Citation for published version (APA): Survery, S. (2015). Characterization of Membrane Proteins: From a gated plant aquaporin to animal ion channel receptors. Department of Biochemistry and Structural Biology, Lund University. Total number of authors: 1 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Printed by Media-Tryck, Lund University 2015 SURVERY SABEEN Characterization of Membrane Proteins - From a gated plant aquaporin to animal ion channel
    [Show full text]