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potassium reposition

Mark A Corbett, Susannah T Bellows, Melody Li, Renée Carroll, Silvana Micallef, Gemma L Carvill, Candace T Myers, Katherine B Howell, Snezana Maljevic, Holger Lerche, Elena V Gazina, Heather C Mefford, Melanie Bahlo, Samuel F Berkovic, Steven Petrou, Ingrid E Scheffer, Jozef Gecz
OBJECTIVE: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. METHODS: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations...
October 12, 2016: Neurology
Luigi Leanza, Antonella Managò, Mario Zoratti, Erich Gulbins, Ildiko Szabo
Since the discovery of the participation of various ion channels in the regulation of cell proliferation and programmed cell death two decades ago, the field exploring ion channel function in relation to cancer has undergone rapid development. Although the mechanisms accounting for the impact of ion channel modulators on cancer growth have not been fully clarified in all cases, numerous in vivo experiments targeting diverse ion channels in various cancer models illustrate the great potentiality of this approach and promote ion channels to the class of oncological targets...
June 2016: Biochimica et Biophysica Acta
Giordano F Z da Silva, Brandon R Goblirsch, Ah-Lim Tsai, John L Spudich
A recently discovered rhodopsin ion pump (DeNaR, also known as KR2) in the marine bacterium Dokdonia eikasta uses light to pump protons or sodium ions from the cell depending on the ionic composition of the medium. In cells suspended in a KCl solution, DeNaR functions as a light-driven proton pump, whereas in a NaCl solution, DeNaR conducts light-driven sodium ion pumping, a novel activity within the rhodopsin family. These two distinct functions raise the questions of whether the conformations of the protein differ in the presence of K(+) or Na(+) and whether the helical movements that result in the canonical E → C conformational change in other microbial rhodopsins are conserved in DeNaR...
June 30, 2015: Biochemistry
Olga Kinclova-Zimmermannova, Pierre Falson, Denis Cmunt, Hana Sychrova
Na(+)/H(+) antiporters may recognize all alkali-metal cations as substrates but may transport them selectively. Plasma-membrane Zygosaccharomyces rouxii Sod2-22 antiporter exports Na(+) and Li(+), but not K(+). The molecular basis of this selectivity is unknown. We combined protein structure modeling, site-directed mutagenesis, phenotype analysis and cation efflux measurements to localize and characterize the cation selectivity region. A three-dimensional model of the ZrSod2-22 transmembrane domain was generated based on the X-ray structure of the Escherichia coli NhaA antiporter and primary sequence alignments with homologous yeast antiporters...
April 24, 2015: Journal of Molecular Biology
Eriko Kikuchi, Takayasu Mori, Moko Zeniya, Kiyoshi Isobe, Mari Ishigami-Yuasa, Shinya Fujii, Hiroyuki Kagechika, Tomoaki Ishihara, Tohru Mizushima, Sei Sasaki, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Upon activation by with-no-lysine kinases, STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na(+)-Cl(-) cotransporter (NCC) and Na(+)-K(+)-2Cl(-) cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively...
July 2015: Journal of the American Society of Nephrology: JASN
J N Mirchandani Jagwani, R Arias Rico
INTRODUCTION: Fluid therapy is one of the most common daily practices although knowledge is necessary on electrolytes and fluids intake and on all the pathophysiologic states leading to fluid homeostasis impairment in order to properly handle the electrolytes for both fluid therapy and parenteral nutrition. OBJECTIVES: To know the content and electrolyte type in those drugs administered through the parenteral route commercialized and authorized in Spain until February of 2012...
March 2013: Farmacia Hospitalaria
Melissa Richard-Lalonde, Karim Nagi, Nicolas Audet, Rory Sleno, Mohammad Amraei, Mireille Hogue, Gianfranco Balboni, Peter W Schiller, Michel Bouvier, Terence E Hébert, Graciela Pineyro
This study assessed how conformational information encoded by ligand binding to δ-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reciprocal interactions among signaling partners. These and coimmunoprecipitation studies indicated that DORs, Gβγ, and Kir3 subunits constitutively interacted with one another. GαoA associated with DORs and Gβγ, but despite being part of the complex, no evidence of its direct association with the channel was obtained...
February 2013: Molecular Pharmacology
David Ehrhardt, Eric Eggenberger
PURPOSE OF REVIEW: This article synthesises recent findings and addresses relevant anatomy, pathophysiologic considerations, and current treatment options for common forms of acquired nystagmus including vestibular and gaze holding dysfunction. RECENT FINDINGS: Some forms of nystagmus have relatively specific treatments, such as baclofen for periodic alternating nystagmus, and repositioning for benign paroxysmal positional vertigo. Recent studies have brought changes to many of the treatments of nystagmus variants...
November 2012: Current Opinion in Ophthalmology
Maria N Eliseeva, Lawrence T Scott
Small amounts of base (e.g., 10% potassium t-butoxide or sodium methoxide) have been found to promote equilibration of the kinetically favored products from Ir-catalyzed C-H polyborylations of aromatic compounds. In the presence of excess borylating agent, bis(pinacolato)diborane (B(2)pin(2)), repetitive deborylation/reborylations reposition the Bpin substituents until a pattern that accommodates the maximum number of Bpin substituents is achieved. A high-yield, one-step synthesis of 1,3,5,7,9-pentakis(Bpin)corannulene is reported that illustrates this useful extension of the Ir-catalyzed borylation reaction...
September 19, 2012: Journal of the American Chemical Society
Izumi Maezawa, David Paul Jenkins, Benjamin E Jin, Heike Wulff
There exists an urgent need for new target discovery to treat Alzheimer's disease (AD); however, recent clinical trials based on anti-Aβ and anti-inflammatory strategies have yielded disappointing results. To expedite new drug discovery, we propose reposition targets which have been previously pursued by both industry and academia for indications other than AD. One such target is the calcium-activated potassium channel KCa3.1 (KCNN4), which in the brain is primarily expressed in microglia and is significantly upregulated when microglia are activated...
2012: International Journal of Alzheimer's Disease
Alan Talevi, Andrea V Enrique, Luis E Bruno-Blanch
A virtual screening campaign based on application of a topological discriminant function capable of identifying novel anticonvulsant agents indicated several widely-used artificial sweeteners as potential anticonvulsant candidates. Acesulfame potassium, cyclamate and saccharin were tested in the Maximal Electroshock Seizure model (mice, ip), showing moderate anticonvulsant activity. We hypothesized a probable structural link between the receptor responsible of sweet taste and anticonvulsant molecular targets...
June 15, 2012: Bioorganic & Medicinal Chemistry Letters
Hye Joo Kim, Mikyung Park, Young-Min Han, Byoung-Mog Kwon, Seong Hwan Kim
As the primary step for 'drug repositioning', we evaluated the effect of 2000 drugs and drug candidates on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP)-2 and found that butamben enhanced BMP-2-stimulated induction of alkaline phosphatase, a biomarker of osteoblastogenesis. Investigating the underlying mechanism of its anabolic actions, we found anabolic action of its derivative (compound 4) relies on BMP-2 signaling and mRNA induction of BMPs and voltage-gated potassium channels...
December 15, 2011: Bioorganic & Medicinal Chemistry Letters
Joel A Butterwick, Roderick MacKinnon
Voltage-sensor domains (VSDs) are specialized transmembrane segments that confer voltage sensitivity to many proteins such as ion channels and enzymes. The activities of these domains are highly dependent on both the chemical properties and the physical properties of the surrounding membrane environment. To learn about VSD-lipid interactions, we used nuclear magnetic resonance spectroscopy to determine the structure and phospholipid interface of the VSD from the voltage-dependent K(+) channel KvAP (prokaryotic Kv from Aeropyrum pernix)...
November 5, 2010: Journal of Molecular Biology
James J Chambers, Richard H Kramer
Light-activated ion channels provide a new opportunity to precisely and remotely control neuronal activity for experimental applications in neurobiology. In the past few years, several strategies have arisen that allow light to control ion channels and therefore neuronal function. Light-based triggers for ion channel control include caged compounds, which release active neurotransmitters when photolyzed with light, and natural photoreceptive proteins, which can be expressed exogenously in neurons. More recently, a third type of light trigger has been introduced: a photoisomerizable tethered ligand that directly controls ion channel activity in a light-dependent manner...
2008: Methods in Cell Biology
A L Green, J E Lombard, L P Garber, B A Wagner, G W Hill
The primary objective of this study was to compare characteristics of US dairy operations that had one or more nonambulatory cows (unable to rise for any period of time) (cases) with operations that had no nonambulatory cows (controls) during 2004. A secondary objective was to describe factors associated with recovery of the last nonambulatory cow on the operation during 2004. Case dairy operations (n = 1,822) more often fed a total mixed ration [odds ratio (OR) = 2.0; confidence interval (CI): 1.1-3.4], produced more than 9,090 kg of milk (OR = 2...
June 2008: Journal of Dairy Science
Jesse J L Chew, Liliana Werner, Gary Mackman, Nick Mamalis
A 55-year-old man had uneventful phacoemulsification with implantation of a 3-piece silicone intraocular lens (IOL). Postoperative medications included antibiotic-steroid drops and ointments. Eight months postoperatively, the patient started having recurrent episodes of anterior chamber inflammatory reaction. Suspicion that lens instability was causing the reactions led to a lens repositioning procedure 11 months after the initial surgical implantation and again at 13 months. Eighteen months postoperatively, the IOL had a "greasy" film...
February 2006: Journal of Cataract and Refractive Surgery
Mehmet Cudi Balkaya, Aynur Cinar, Selim Pamuk
STATEMENT OF PROBLEM: Although all-ceramic restorations are widely used, there is a lack of information about how the fit is affected by fabrication procedures. The adequacy of the fit of all-ceramic restorations has been questioned. PURPOSE: This study examined the effect of porcelain and glaze firing cycles on the fit of 3 types of all-ceramic crowns. MATERIAL AND METHODS: Ten standardized all-ceramic crowns were fabricated on a metal die from each of 3 systems: conventional In-Ceram, copy-milled In-Ceram, and copy-milled feldspathic crowns...
April 2005: Journal of Prosthetic Dentistry
V Mehta, Z Ahmed
Blood samples were obtained from a radial artery cannula in a 60-yr-old man during coronary artery surgery. Serum potassium concentrations of 9.3, 8.4, and 7.4 mmol litre(-1) were obtained. A simultaneous venous blood sample gave a serum potassium concentration of 4.4 mmol litre(-1). The ECG was unchanged. After the arterial cannula was repositioned, subsequent blood samples gave expected ranges of serum potassium concentration. We suggest that the initial arterial cannula position caused a high shear rate in the blood when samples were withdrawn, causing haemolysis and hyperkalaemia...
September 2004: British Journal of Anaesthesia
John S Mitcheson, Matthew D Perry
Human ether-a-go-go-related gene (HERG) subunits mediate a K+ current that is required for normal repolarization of the cardiac action potential. The unintentional inhibition of HERG currents by numerous medications results in prolongation of the QT interval, as measured on the electrocardiogram, and is associated with increased risk of patients suffering from life-threatening cardiac arrhythmias. QT interval prolongation is considered a major safety concern by worldwide drug regulatory bodies, and early detection of new compounds with this undesirable side effect has become an important objective for pharmaceutical companies...
September 2003: Current Opinion in Drug Discovery & Development
Adam Kohn, Carol Metz, Mark A Tommerdahl, Barry L Whitsel
Sensory cortical neurons display substantial receptive field dynamics during and after persistent sensory drive. Because a cell's response properties are determined by the inputs it receives, receptive field dynamics are likely to involve changes in the relative efficacy of different inputs to the cell. To test this hypothesis, we have investigated if brief repetitive stimulus drive in vitro alters the efficacy of two types of corticocortical inputs to layer V pyramidal cells. Specifically, we have used whole cell recordings to measure the effect of repetitive electrical stimulation at the layer VI/white matter (WM) border on the synaptic response of layer V pyramidal cells to corticocortical input evoked by electrical stimulation of layer I or layer II/III and emulated by local application of glutamate...
December 2002: Journal of Neurophysiology
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