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https://www.readbyqxmd.com/read/29677462/ondansetron-blocks-wildtype-and-p-f503l-variant-small-conductance-calcium-activated-potassium-channels
#1
Jum-Suk Ko, Shuai Guo, Jonathan Hassel, Patricia Celestino-Soper, Ty C Lynnes, James E Tisdale, James J Zheng, Stanley E Taylor, Tatiana Foroud, Michael D Murray, Richard J Kovacs, Xiaochun Li, Shien-Fong Lin, Zhenhui Chen, Matteo Vatta, Peng-Sheng Chen, Michael Rubart
The apamin-sensitive, small conductance, calcium-activated potassium (SK) current ( IKAS ) is encoded by KCNN genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT (diLQT) syndrome, we (1) screened for KCNN variants among patients with diLQT, (2) determined the properties of heterologously expressed wildtype and variant KCNN channels, and (3) determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS ...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29675256/a-case-with-relapsed-transient-neonatal-diabetes-mellitus-treated-with-sulfonylurea-ending-chronic-insulin-requirement
#2
Akihiko Ando, Shoichiro Nagasaka, Shun Ishibashi
We report a case of a woman with diabetes mellitus caused by a genetic defect in ABCC8 -coding sulfonylurea receptor 1 (SUR1), a subunit of the ATP-sensitive potassium (KATP ) channel protein. She was diagnosed with diabetes at 7 days after birth. After intravenous insulin drip for 1 month, her hyperglycaemia remitted. At the age of 13 years, her diabetes relapsed, and after that she had been treated by intensive insulin therapy for 25 years with relatively poor glycaemic control. She was switched to oral sulfonylurea therapy and attained euglycaemia...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29674690/ultrasound-activated-piezoelectric-nanoparticles-inhibit-proliferation-of-breast-cancer-cells
#3
Attilio Marino, Matteo Battaglini, Daniele De Pasquale, Andrea Degl'Innocenti, Gianni Ciofani
A nanotechnology-based approach for the inhibition of breast cancer cell proliferation is proposed. The innovative solution consists in a platform based on biocompatible piezoelectric nanoparticles able to target and remotely stimulate HER2-positive breast cancer cells. The anti-proliferative effects of the ultrasound-driven piezoelectric nanoparticle-assisted stimulation significantly reduced the proliferation by inducing the cell cycle arrest. Similarly to a low-intensity alternating electric field, chronic piezoelectric stimulation resulted able to inhibit cancer cell proliferation by upregulating the expression of the gene encoding Kir3...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29674667/a-mixed-periodic-paralysis-myotonia-mutant-p1158s-imparts-ph-sensitivity-in-skeletal-muscle-voltage-gated-sodium-channels
#4
Mohammad-Reza Ghovanloo, Mena Abdelsayed, Colin H Peters, Peter C Ruben
Skeletal muscle channelopathies, many of which are inherited as autosomal dominant mutations, include myotonia and periodic paralysis. Myotonia is defined by a delayed relaxation after muscular contraction, whereas periodic paralysis is defined by episodic attacks of weakness. One sub-type of periodic paralysis, known as hypokalemic periodic paralysis (hypoPP), is associated with low potassium levels. Interestingly, the P1158S missense mutant, located in the third domain S4-S5 linker of the "skeletal muscle", Nav1...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29674316/activation-of-renal-clc-k-chloride-channels-depends-on-an-intact-n-terminus-of-their-accessory-subunit-barttin
#5
Daniel Wojciechowski, Stefan Thiemann, Christina Schaal, Alina Rahtz, Jeanne de la Roche, Birgit Begemann, Toni Becher, Martin Fischer
ClC-K channels belong to the CLC family of chloride channels and chloride/proton antiporters. They contribute to sodium chloride reabsorption in Henle's loop of the kidney and to potassium secretion into the endolymph by the stria vascularis of the inner ear. Their accessory subunit barttin stabilizes the ClC-K/barttin complex, promotes its insertion into the surface membrane, and turns the pore-forming subunits into a conductive state. Barttin mutations cause Bartter syndrome type IV, a salt wasting nephropathy with sensorineural deafness...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29671888/whole-exome-sequencing-reveals-microsatellites-dna-markers-for-response-to-dofetilide-initiation-in-patients-with-persistent-atrial-fibrillation-a-pilot-study
#6
Nick Kinney, Timothy R Larsen, David M Kim, Robin T Varghese, Steven Poelzing, Harold R Garner, Soufian T AlMahameed
BACKGROUND: Dofetilide is a class III antiarrhythmic drug effective for the treatment of atrial fibrillation (AF). Dofetilide initiation (DI) associate with corrected QT (QTc) interval prolongation. Significant QTc prolongation during DI mandates dose adjustment or discontinuation of the drug. Microsatellite DNA are novel genetic markers associate with congenital and acquired health conditions. OBJECTIVE: The purpose of this study was to explore potential genetic markers for QTc prolongation in response to DI in patients with persistent AF METHODS: We performed Whole Exome sequencing in a cohort of patients with persistent AF undergoing DI...
April 19, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29671418/the-role-of-k-atp-channels-in-cerebral-ischemic-stroke-and-diabetes
#7
REVIEW
Vivian Szeto, Nai-Hong Chen, Hong-Shuo Sun, Zhong-Ping Feng
ATP-sensitive potassium (KATP ) channels are ubiquitously expressed on the plasma membrane of cells in multiple organs, including the heart, pancreas and brain. KATP channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are inhibited by ATP and activated by Mg-ADP, allowing the cell to couple cellular metabolic state (ATP/ADP ratio) to electrical activity of the cell membrane. KATP channels mediate insulin secretion in pancreatic islet beta cells, and controlling vascular tone...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29671323/in-situ-visualization-of-herg-potassium-channel-via-dual-signal-amplification
#8
Xue-Jiao Yang, Kai Zhang, Hong-Yuan Chen, Jing-Juan Xu
Dysfunction of the human ether-a-go-go related gene (hERG)-encoded potassium channel is identified as a major cause of the long Q-T syndrome, a marker for the lethal cardiac arrhythmia. Furthermore, recent studies revealed that hERG K+ channel is a regulator of tumor cell apoptosis and proliferation. Herein, an ultrasensitive fluorescence assay combining DNA-functionalized gold nanoparticles and rolling circle amplification (RCA) is first attempted to visualize hERG channels in living cells. The spherical nucleic acids gold nanoparticles which can anchor on hERG channels in the cell membrane, not only act as the primary amplification elements, but also trigger the subsequent RCA reaction to achieve the secondary amplification...
April 19, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29670409/safinamide-an-add-on-treatment-for-managing-parkinson-s-disease
#9
REVIEW
Thomas Müller
Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson's disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These "OFF" states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with "OFF" phenomena...
2018: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29670283/genetic-identification-of-leptin-neural-circuits-in-energy-and-glucose-homeostases
#10
Jie Xu, Christopher L Bartolome, Cho Shing Low, Xinchi Yi, Cheng-Hao Chien, Peng Wang, Dong Kong
Leptin, a hormone produced in white adipose tissue, acts in the brain to communicate fuel status, suppress appetite following a meal, promote energy expenditure and maintain blood glucose stability1,2 . Dysregulation of leptin or its receptors (LEPR) results in severe obesity and diabetes3-5 . Although intensive studies on leptin have transformed obesity and diabetes research2,6 , clinical applications of the molecule are still limited 7 , at least in part owing to the complexity and our incomplete understanding of the underlying neural circuits...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29669989/chronic-manganese-toxicity-associated-with-voltage-gated-potassium-channel-complex-antibodies-in-a-relapsing-neuropsychiatric-disorder
#11
Cyrus S H Ho, Roger C M Ho, Amy M L Quek
Heavy metal poisoning is a rare but important cause of encephalopathy. Manganese (Mn) toxicity is especially rare in the modern world, and clinicians’ lack of recognition of its neuropsychiatric manifestations can lead to misdiagnosis and mismanagement. We describe the case of a man who presented with recurrent episodes of confusion, psychosis, dystonic limb movement and cognitive impairment and was initially diagnosed with anti-voltage-gated potassium channel (VGKC) complex limbic encephalitis in view of previous positive autoantibodies...
April 18, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29669325/characterization-of-the-%C3%AF-pore-in-mutant-hkv1-3-potassium-channels
#12
Pavel Tyutyaev, Stephan Grissmer
BACKGROUND/AIMS: The replacement of the amino acid valine at position 388 (Shaker position 438) in hKv1.3 channels or at the homologue position 370 in hKv1.2 channels resulted in a channel with two different ion conducting pathways: One pathway was the central, potassium-selective α-pore, that was sensitive to block by peptide toxins (CTX or KTX in the hKv1.3_V388C channel and CTX or MTX in the hKv1.2_V370C channel). The other pathway (σ-pore) was behind the central α-pore creating an inward current at potentials more negative than -100 mV, a potential range where the central α-pore was closed...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29669276/tmem150c-tentonin3-is-a-regulator-of-mechano-gated-ion-channels
#13
Evan O Anderson, Eve R Schneider, Jon D Matson, Elena O Gracheva, Sviatoslav N Bagriantsev
Neuronal mechano-sensitivity relies on mechano-gated ion channels, but pathways regulating their activity remain poorly understood. TMEM150C was proposed to mediate mechano-activated current in proprioceptive neurons. Here, we studied functional interaction of TMEM150C with mechano-gated ion channels from different classes (Piezo2, Piezo1, and the potassium channel TREK-1) using two independent methods of mechanical stimulation. We found that TMEM150C significantly prolongs the duration of the mechano-current produced by all three channels, decreases apparent activation threshold in Piezo2, and induces persistent current in Piezo1...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29668858/densities-and-laminar-distributions-of-kv3-1b-pv-gaba-and-smi-32-immunoreactive-neurons-in-macaque-area-v1
#14
Jenna G Kelly, Virginia García-Marín, Bernardo Rudy, Michael J Hawken
The Kv3.1b potassium channel subunit is associated with narrow spike widths and fast-spiking properties. In macaque primary visual cortex (V1), subsets of neurons have previously been found to be Kv3.1b-immunoreactive (ir) but not parvalbumin (PV)-ir or not GABA-ir, suggesting that they may be both fast-spiking and excitatory. This population includes Meynert cells, the large layer 5/6 pyramidal neurons that are also labeled by the neurofilament antibody SMI-32. In the present study, triple immunofluorescence labeling and confocal microscopy were used to measure the distribution of Kv3...
April 13, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29668703/activation-of-host-transient-receptor-potential-trp-channels-by-praziquantel-stereoisomers
#15
Gihan S Gunaratne, Nawal Yahya, Peter I Dosa, Jonathan S Marchant
The anthelmintic praziquantel (±PZQ) serves as a highly effective antischistosomal therapy. ±PZQ causes a rapid paralysis of adult schistosome worms and deleterious effects on the worm tegument. In addition to these activities against the parasite, ±PZQ also modulates host vascular tone in blood vessels where the adult worms reside. In resting mesenteric arteries ±PZQ causes a constriction of basal tone, an effect mediated by (R)-PZQ activation of endogenous serotoninergic G protein coupled receptors (GPCRs)...
April 18, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29666984/unusual-white-matter-involvement-in-east-syndrome-associated-with-novel-kcnj10-mutations
#16
Mariasavina Severino, Susanna Lualdi, Chiara Fiorillo, Pasquale Striano, Teresa De Toni, Silvio Peluso, Giuseppe De Michele, Andrea Rossi, Mirella Filocamo, Claudio Bruno
BACKGROUND: Epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) is a rare channelopathy due to KCNJ10 mutations. So far, only mild cerebellar hypoplasia and/or dentate nuclei abnormalities have been reported as major neuroimaging findings in these patients. METHODS: We analyzed the clinical and brain MRI features of two unrelated patients (aged 27 and 23 years) with EAST syndrome carrying novel homozygous frameshift mutations (p.Asn232Glnfs*14and p...
April 17, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29666184/atp-sensitive-potassium-channels-in-the-sinoatrial-node-contribute-to-heart-rate-control-and-adaptation-to-hypoxia
#17
Qadeer Aziz, Malcolm Finlay, David Montaigne, Leona Ojake, Yiwen Li, Naomi Anderson, Andreas Ludwig, Andrew Tinker
ATP-sensitive potassium channels (KATP ) contribute to membrane currents in many tissues, are responsive to intracellular metabolism, and open as ATP falls and ADP rises. KATP channels are widely distributed in tissues and are prominently expressed in the heart. They have generally been observed in ventricular tissue, but they are also expressed in the atria and conduction tissues. In this study, we focused on the contribution and role of the inwardly rectifying KATP channel subunit, Kir6.1, in the sinoatrial node (SAN)...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29665277/the-expression-of-endogenous-voltage-gated-potassium-channels-in-hek293-cells-is-affected-by-culture-conditions
#18
Arturo Ponce, Aida Castillo, Lorena Hinojosa, Jacqueline Martinez-Rendon, Marcelino Cereijido
HEK293 cells are widely used as a host for expression of heterologous proteins; yet, little care has been taken to characterize their endogenous membrane components, including ion channels. In this work, we aimed to describe the biophysical and pharmacological properties of endogenous, voltage-dependent potassium currents (IKv). We also examined how its expression depends on culture conditions. We used the electrophysiological technique of whole-cell patch clamp to record ion currents from HEK293 cells. We found that HEK cells express endogenous, voltage-dependent potassium currents...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29660559/potassium-dynamics-and-seizures-why-is-potassium-ictogenic
#19
REVIEW
Marco de Curtis, Laura Uva, Vadym Gnatkovsky, Laura Librizzi
Potassium channels dysfunction and altered genes encoding for molecules involved in potassium homeostasis have been associated with human epilepsy. These observations are in agreement with a control role of extracellular potassium on neuronal excitability and seizure generation. Epileptiform activity, in turn, regulates potassium homeostasis through mechanisms that are still not well established. We review here how potassium-associated processes are regulated in the brain and examine the mechanisms that support the role of potassium in triggering epileptiform activities...
April 10, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29660155/thread-paper-and-paper-based-microfluidic-devices-for-glucose-assays-employing-artificial-neural-networks
#20
Wilson Lee, Ariana Gonzalez, Paolo Arguelles, Ricardo Guevara, Maria Jose Gonzalez-Guerrero, Frank A Gomez
This paper describes the fabrication of and data collection from two microfluidic devices: a microfluidic thread/paper based analytical device (μTPAD) and 3D microfluidic paper-based analytical device (μPAD). Flowing solutions of glucose oxidase (GOx), horseradish peroxidase (HRP), and potassium iodide (KI), through each device, on contact with glucose, generated a calibration curve for each platform. The resultant yellow-brown color from the reaction indicates oxidation of iodide to iodine. The devices were dried, scanned, and analyzed yielding a correlation between yellow intensity and glucose concentration...
April 16, 2018: Electrophoresis
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