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KIR4.1

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https://www.readbyqxmd.com/read/28345117/inwardly-rectifying-k-currents-in-cultured-oligodendrocytes-from-rat-optic-nerve-are-insensitive-to-ph
#1
Alberto Pérez-Samartín, Edith Garay, Juan Pablo H Moctezuma, Abraham Cisneros-Mejorado, María Victoria Sánchez-Gómez, Guadalupe Martel-Gallegos, Leticia Robles-Martínez, Manuel Canedo-Antelo, Carlos Matute, Rogelio O Arellano
Inwardly rectifying K(+) (Kir) channel expression signals at an advanced stage of maturation during oligodendroglial differentiation. Knocking down their expression halts the generation of myelin and produces severe abnormalities in the central nervous system. Kir4.1 is the main subunit involved in the tetrameric structure of Kir channels in glial cells; however, the precise composition of Kir channels expressed in oligodendrocytes (OLs) remains partially unknown, as participation of other subunits has been proposed...
March 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28300540/detection-of-potassium-channel-kir4-1-antibodies-in-multiple-sclerosis-patients
#2
Fabiana Marnetto, Paola Valentino, Marzia Caldano, Antonio Bertolotto
The presence of KIR4.1 antibodies has been proposed to be a characteristic of Multiple Sclerosis (MS). This could have a significant impact on disease management. However, the validation of the initial findings has failed till date. Conflicting results have been attributed to difficulties in isolating the lower-glycosylated (LG) KIR4.1 expressed in oligodendrocytes, the putative target antigen of autoantibodies. The aim of this study is to verify the presence of KIR4.1 antibodies in MS patients, by independently replicating the originally-described procedure...
March 11, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28297725/rearing-light-intensity-affects-inner-retinal-pathology-in-a-mouse-model-of-x-linked-retinoschisis-but-does-not-alter-gene-therapy-outcome
#3
Dario Marangoni, Zeng Yong, Sten Kjellström, Camasamudram Vijayasarathy, Paul A Sieving, Ronald A Bush
Purpose: To test the effects of rearing light intensity on retinal function and morphology in the retinoschisis knockout (Rs1-KO) mouse model of X-linked retinoschisis, and whether it affects functional outcome of RS1 gene replacement. Methods: Seventy-six Rs1-KO mice were reared in either cyclic low light (LL, 20 lux) or moderate light (ML, 300 lux) and analyzed at 1 and 4 months. Retinal function was assessed by electroretinogram and cavity size by optical coherence tomography...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28288868/inhibition-of-kir4-1-potassium-channels-by-quinacrine
#4
Leticia G Marmolejo-Murillo, Iván A Aréchiga-Figueroa, Meng Cui, Eloy G Moreno-Galindo, Ricardo A Navarro-Polanco, José A Sánchez-Chapula, Tania Ferrer, Aldo A Rodríguez Menchaca
Inwardly rectifying potassium (Kir) channels are expressed in many cell types and contribute to a wide range of physiological processes. Particularly, Kir4.1 channels are involved in the astroglial spatial potassium buffering. In this work, we examined the effects of the cationic amphiphilic drug quinacrine on Kir4.1 channels heterologously expressed in HEK293 cells, employing the patch clamp technique. Quinacrine inhibited the currents of Kir4.1 channels in a concentration and voltage dependent manner. In inside-out patches, quinacrine inhibited Kir4...
March 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28270749/identifying-candidate-genes-that-underlie-cellular-ph-sensitivity-in-serotonin-neurons-using-transcriptomics-a-potential-role-for-kir5-1-channels
#5
Madeleine M Puissant, Gary C Mouradian, Pengyuan Liu, Matthew R Hodges
Ventilation is continuously adjusted by a neural network to maintain blood gases and pH. Acute CO2 and/or pH regulation requires neural feedback from brainstem cells that encode CO2/pH to modulate ventilation, including but not limited to brainstem serotonin (5-HT) neurons. Brainstem 5-HT neurons modulate ventilation and are stimulated by hypercapnic acidosis, the sensitivity of which increases with increasing postnatal age. The proper function of brainstem 5-HT neurons, particularly during post-natal development is critical given that multiple abnormalities in the 5-HT system have been identified in victims of Sudden Infant Death Syndrome...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28216048/chloroquine-blocks-the-kir4-1-channels-by-an-open-pore-blocking-mechanism
#6
Leticia G Marmolejo-Murillo, Iván A Aréchiga-Figueroa, Eloy G Moreno-Galindo, Ricardo A Navarro-Polanco, Aldo A Rodríguez-Menchaca, Meng Cui, José A Sánchez-Chapula, Tania Ferrer
Kir4.1 channels have been implicated in various physiological processes, mainly in the K(+) homeostasis of the central nervous system and in the control of glial function and neuronal excitability. Even though, pharmacological research of these channels is very limited. Chloroquine (CQ) is an amino quinolone derivative known to inhibit Kir2.1 and Kir6.2 channels with different action mechanism and binding site. Here, we employed patch-clamp methods, mutagenesis analysis, and molecular modeling to characterize the molecular pharmacology of Kir4...
April 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28214987/severe-convulsions-and-dysmyelination-in-both-jimpy-and-cx32-47-mice-may-associate-astrocytic-l-channel-function-with-myelination-and-oligodendrocytic-connexins-with-internodal-kv-channels
#7
Y H Gerald Chaban, Ye Chen, Elna Hertz, Leif Hertz
The Jimpy mouse illustrates the importance of interactions between astrocytes and oligodendrocytes. It has a mutation in Plp coding for proteolipid protein and DM20. Its behavior is normal at birth but from the age of ~2 weeks it shows severe convulsions associated with oligodendrocyte/myelination deficits and early death. A normally occurring increase in oxygen consumption by highly elevated K(+) concentrations is absent in Jimpy brain slices and cultured astrocytes, reflecting that Plp at early embryonic stages affects common precursors as also shown by the ability of conditioned medium from normal astrocytes to counteract histological abnormalities...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28159978/protection-of-glial-m%C3%A3-ller-cells-by-dexamethasone-in-a-mouse-model-of-surgically-induced-blood-retinal-barrier-breakdown
#8
Lourdes Siqueiros-Marquez, Romain Bénard, Ophélie Vacca, Hugo Charles-Messance, Rodrigo Bolaños-Jimenez, Xavier Guilloneau, Florian Sennlaub, Cecilia Montañez, José Alain Sahel, Alvaro Rendon, Ramin Tadayoni, Audrey Giocanti-Aurégan
Purpose: Breakdown of the inner blood-retinal barrier (iBRB) occurs in many retinal disorders and may cause retinal edema often responsible for vision loss. Dexamethasone is used in clinical practice to restore iBRB. The aim of this study was to characterize the impact of a surgically induced iBRB breakdown on retinal homeostatic changes due to dystrophin Dp71, aquaporin-4 (AQP4), and Kir4.1 alterations in Müller glial cells (MGC) in a mouse model. The protective effect of dexamethasone was assessed in this model...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28067240/cd8-t-cells-stimulate-na-cl-co-transporter-ncc-in-distal-convoluted-tubules-leading-to-salt-sensitive-hypertension
#9
Yunmeng Liu, Tonya M Rafferty, Sung W Rhee, Jessica S Webber, Li Song, Benjamin Ko, Robert S Hoover, Beixiang He, Shengyu Mu
Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8(+) T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8(+) T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28052988/potassium-sensing-by-renal-distal-tubules-requires-kir4-1
#10
Catherina A Cuevas, Xiao-Tong Su, Ming-Xiao Wang, Andrew S Terker, Dao-Hong Lin, James A McCormick, Chao-Ling Yang, David H Ellison, Wen-Hui Wang
The mammalian distal convoluted tubule (DCT) makes an important contribution to potassium homeostasis by modulating NaCl transport. The thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) is activated by low potassium intake and by hypokalemia. Coupled with suppression of aldosterone secretion, activation of NCC helps to retain potassium by increasing electroneutral NaCl reabsorption, therefore reducing Na(+)/K(+) exchange. Yet the mechanisms by which DCT cells sense plasma potassium concentration and transmit the information to the apical membrane are not clear...
January 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27989734/systemic-application-of-aav-vectors-targeting-gfap-expressing-astrocytes-in-z-q175-ki-huntington-s-disease-mice
#11
Tatyana Vagner, Anton Dvorzhak, Anna Maria Wójtowicz, Christoph Harms, Rosemarie Grantyn
Huntington's disease (HD) affects both neurons and astrocytes. To target the latter and to ensure brain-wide transgene expression, adeno-associated viral (AAV) vectors can be administered intravenously, as AAV vectors cross the blood-brain barrier (BBB) and enable preferential transduction of astrocytes due to their close association with blood vessels. However, there is a possibility that the subclass of GFAP-expressing astrocytes performs a distinct role in HD and reacts differently to therapeutic measures than the rest of the astrocytes...
October 27, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27965079/diversity-of-astrocyte-potassium-channels-an-update
#12
REVIEW
Gerald Seifert, Christian Henneberger, Christian Steinhäuser
Astrocyte K(+) channels and the K(+) currents they mediate dwarf all other transmembrane conductances in these cells. This defining feature of astrocytes and its functional implications have been investigated intensely over the past decades. Nonetheless, many aspects of astrocyte K(+) handling and signaling remain incompletely understood. In this review, we provide an update on the diversity of K(+) channels expressed by astrocytes and new functional implications. We focus on inwardly-rectifying K(+) channels (particularly Kir4...
December 11, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27890830/time-course-of-glial-changes-in-the-hyperhomocysteinemia-model-of-vascular-cognitive-impairment-and-dementia-vcid
#13
Tiffany L Sudduth, Erica M Weekman, Brittani R Price, Jennifer L Gooch, Abigail Woolums, Christopher M Norris, Donna M Wilcock
Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent co-morbidity with AD. Despite its prevalence, little is known about the molecular mechanisms underlying the cognitive dysfunction resulting from cerebrovascular disease. Astrocytic end-feet almost completely surround intraparenchymal blood vessels in the brain and express a variety of channels and markers indicative of their specialized functions in the maintenance of ionic and osmotic homeostasis and gliovascular signaling...
January 26, 2017: Neuroscience
https://www.readbyqxmd.com/read/27729847/kir4-1-k-channel-illusion-or-reality-in-the-autoimmune-pathogenesis-of-multiple-sclerosis
#14
REVIEW
Chen Gu
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Many believe autoimmune pathogenesis plays a key role in MS, but its target(s) remains elusive. A recent study detected autoantibodies against KIR4.1, an ATP-sensitive, inward rectifier potassium channel, in nearly half of the MS patients examined. KIR4.1 channels are expressed in astrocytes. Together with aquaporin 4 (AQP4) water channels, they regulate astrocytic functions vital for myelination. Autoantibodies against AQP4 have been established as a key biomarker for neuromyelitis optica (NMO) and contributed to diagnostic and treatment strategy adjustments...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27693230/importance-of-astrocytes-for-potassium-ion-k-homeostasis-in-brain-and-glial-effects-of-k-and-its-transporters-on-learning
#15
REVIEW
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...
December 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27680950/molecular-bases-of-k-secretory-cells-in-the-inner-ear-shared-and-distinct-features-between-birds-and-mammals
#16
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
https://www.readbyqxmd.com/read/27677466/gain-of-function-defects-of-astrocytic-kir4-1-channels-in-children-with-autism-spectrum-disorders-and-epilepsy
#17
Federico Sicca, Elena Ambrosini, Maria Marchese, Luigi Sforna, Ilenio Servettini, Giulia Valvo, Maria Stefania Brignone, Angela Lanciotti, Francesca Moro, Alessandro Grottesi, Luigi Catacuzzeno, Sara Baldini, Sonia Hasan, Maria Cristina D'Adamo, Fabio Franciolini, Paola Molinari, Filippo M Santorelli, Mauro Pessia
Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define the role of Kir4.1 variants in the disorder, we sequenced KCNJ10 in a sample of affected individuals, and performed genotype-phenotype correlations. The effects of mutations on channel activity, protein trafficking, and astrocyte function were investigated in Xenopus laevis oocytes, and in human astrocytoma cell lines. An in vivo model of the disorder was also explored through generation of kcnj10a morphant zebrafish overexpressing the mutated human KCNJ10...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27671501/hmg-coa-synthase-isoenzymes-1-and-2-localize-to-satellite-glial-cells-in-dorsal-root-ganglia-and-are-differentially-regulated-by-peripheral-nerve-injury
#18
Fei Wang, Hongfei Xiang, Gregory Fischer, Zhen Liu, Matthew J Dupont, Quinn H Hogan, Hongwei Yu
In dorsal root ganglia (DRG), satellite glial cells (SGCs) tightly ensheathe the somata of primary sensory neurons to form functional sensory units. SGCs are identified by their flattened and irregular morphology and expression of a variety of specific marker proteins. In this report, we present evidence that the 3-hydroxy-3-methylglutaryl coenzyme A synthase isoenzymes 1 and 2 (HMGCS1 and HMGCS2) are abundantly expressed in SGCs. Immunolabeling with the validated antibodies revealed that both HMGCS1 and HMGCS2 are highly colabeled with a selection of SGC markers, including GS, GFAP, Kir4...
December 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27572856/immunopathophysiology-of-pediatric-cns-inflammatory-demyelinating-diseases
#19
Amit Bar-Or, Rogier Q Hintzen, Russell C Dale, Kevin Rostasy, Wolfgang Brück, Tanuja Chitnis
Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric- and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing...
August 30, 2016: Neurology
https://www.readbyqxmd.com/read/27546508/-glutamate-receptor-mediated-retinal-neuronal-injury-in-experimental-glaucoma
#20
Zhong-Feng Wang, Xiong-Li Yang
Glaucoma, the second leading cause of blindness, is a neurodegenerative disease characterized by optic nerve degeneration related to apoptotic death of retinal ganglion cells (RGCs). In the pathogenesis of RGC death following the onset of glaucoma, functional changes of glutamate receptors are commonly regarded as important risk factors. During the past several years, we have explored the mechanisms underlying RGC apoptosis and retinal Müller cell reactivation (gliosis) in a rat chronic ocular hypertension (COH) model...
August 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
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