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voltage gated potassium channel

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https://www.readbyqxmd.com/read/29444113/effects-of-protein-protein-interactions-and-ligand-binding-on-the-ion-permeation-in-kcnq1-potassium-channel
#1
Horia Jalily Hasani, Aravindhan Ganesan, Marawan Ahmed, Khaled H Barakat
The voltage-gated KCNQ1 potassium ion channel interacts with the type I transmembrane protein minK (KCNE1) to generate the slow delayed rectifier (IKs) current in the heart. Mutations in these transmembrane proteins have been linked with several heart-related issues, including long QT syndromes (LQTS), congenital atrial fibrillation, and short QT syndrome. Off-target interactions of several drugs with that of KCNQ1/KCNE1 ion channel complex have been known to cause fatal cardiac irregularities. Thus, KCNQ1/KCNE1 remains an important avenue for drug-design and discovery research...
2018: PloS One
https://www.readbyqxmd.com/read/29436653/upregulation-of-phosphatase-and-tensin-homolog-is-essential-for-the-effect-of-4-aminopyridine-on-a549-cddp-cells
#2
Zhengyi Luo, Jiafeng Wang, Chenglin Li, Yumiao Qiu, Jing Huang, Yujie Huang, Hongli Gu, Bin Wu, Zhe Hu, Yan Zhen
4-aminopyridine (4-AP), a voltage-gated potassium channel blocker, was revealed to possess pro‑apoptotic properties in various types of cancer cells. The present study aimed to explore the effect of 4‑AP on a cisplatin (DDP) resistant lung cancer cell line A549/CDDP and the underlying mechanism by which it had an effect. In the present study, an MTT assay and cell cycle analysis were used to determine that 4‑AP inhibited cell growth in vitro and a tumorigenesis assay in nude mice determined that 4‑AP also inhibited cell growth in vivo...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29429937/a-calmodulin-c-lobe-ca2-dependent-switch-governs-kv7-channel-function
#3
Aram Chang, Fayal Abderemane-Ali, Greg L Hura, Nathan D Rossen, Rachel E Gate, Daniel L Minor
Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation...
February 6, 2018: Neuron
https://www.readbyqxmd.com/read/29415410/functional-role-of-kv1-1-and-kv1-3-channels-in-the-neoplastic-progression-steps-of-three-cancer-cell-lines-elucidated-by-scorpion-peptides
#4
Dorra Aissaoui, Saoussen Mlayah-Bellalouna, Jed Jebali, Zaineb Abdelkafi-Koubaa, Soumaya Souid, Wassim Moslah, Houcemeddine Othman, José Luis, Mohamed ElAyeb, Naziha Marrakchi, Khadija Essafi-Benkhadir, Najet Srairi-Abid
Voltage-gated potassium (Kv) channels are known to play a pivotal role in the progression of various cancer types and considered as new targets for designing anti-cancer therapy. However, the fact that many Kv channels are expressed in different cell lines makes it difficult to ascribe a functional role for a given Kv channel on a specific aspect of the tumorogenesis. In this work, we showed that although both Kv1.1 and Kv1.3 channels are expressed in U87 (glioblastoma), MDA-MB-231 (breast cancer) and LS174 (colon adenocarcinoma) cells, these respond differently to KAaH1 or KAaH2, two homologous Kv1 blockers from scorpion venom...
February 2, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29414882/phcrtx2-a-new-crab-paralyzing-peptide-toxin-from-the-sea-anemone-phymanthus-crucifer
#5
Armando Alexei Rodríguez, Anoland Garateix, Emilio Salceda, Steve Peigneur, André Junqueira Zaharenko, Tirso Pons, Yúlica Santos, Roberto Arreguín, Ludger Ständker, Wolf-Georg Forssmann, Jan Tytgat, Rosario Vega, Enrique Soto
Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC) inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis...
February 7, 2018: Toxins
https://www.readbyqxmd.com/read/29393345/slc35e3-identified-as-a-target-of-novel%C3%A2-m1061%C3%A2-5p-via-microrna-profiling-of-patients-with-cardiovascular-disease
#6
Feng Gao, Fa-Gang Wang, Ren-Rong Lyu, Feng Xue, Jian Zhang, Ran Huo
MicroRNAs (miRNA) are considered to be potential therapeutic targets for the treatment of various cardiovascular diseases (CVDs). To understand the underlying mechanism of miRNAs and target genes associated with CVD, deep sequencing of blood samples from three patients with CVD and three controls was performed using the Illumina HiSeq 2000 system. The results of the present study revealed that 65 abnormal hsa‑miRNAs targeted 2,784 putative genes in patients with CVD; 59 upregulated miRNAs targeted 2,401 genes and six downregulated miRNAs targeted 383 genes...
January 25, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29386157/vitex-negundo-induces-an-anticonvulsant-effect-by-inhibiting-voltage-gated-sodium-channels-in-murine-neuro-2a-cell-line
#7
Faisal Khan, Zafar Saeed Saify, Khawar Saeed Jamali, Saima Naz, Sohail Hassan, Sonia Siddiqui
Vitex negundo (Vn) extract is famous for the treatment of neurological diseases such as migraine and epilepsy. These neurological diseases have been associated with abnormally increased influx of sodium ions into the neurons. Drugs that inhibit voltage gated sodium channels can be used as potent anti-epileptics. Till now, the effects of Vn on sodium channels have not been investigated. Therefore, we have investigated the effects of methalonic fraction of Vn extract in Murine Neuro 2A cell line. Cells were cultured in a defined medium with or without the Vn extract (100 μg/ml)...
January 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29383177/a-novel-kcnd3-mutation-associated-with-early-onset-lone-atrial-fibrillation
#8
Yuan Huang, Jiawei Yang, Wanyi Xie, Qince Li, Zhipeng Zeng, Haibo Sui, Zhonggui Shan, Zhengrong Huang
Atrial fibrillation (AF) is the most common arrhythmia in the clinic. While previous studies have identified AF-associated mutations in several genes, the genetic basis for AF remains unclear. Here, we identified a novel T361S missense mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) from a Chinese Han family ancestor with lone AF. The wild-type (WT) or mutant T361S of Kv4.3 protein (encoded by KCND3) were co-expressed with the auxiliary subunit K+ channel-Interacting Protein (KChIP2) in HEK293 cells, and transient outward potassium current (Ito) were recorded using patch-clamp methods, and the surface or total protein levels of Kv4...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29379118/regulation-of-kv2-1-channel-inactivation-by-phosphatidylinositol-4-5-bisphosphate
#9
Mayra Delgado-Ramírez, José J De Jesús-Pérez, Iván A Aréchiga-Figueroa, Jorge Arreola, Scott K Adney, Carlos A Villalba-Galea, Diomedes E Logothetis, Aldo A Rodríguez-Menchaca
Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane phospholipid that regulates the function of multiple ion channels, including some members of the voltage-gated potassium (Kv) channel superfamily. The PIP2 sensitivity of Kv channels is well established for all five members of the Kv7 family and for Kv1.2 channels; however, regulation of other Kv channels by PIP2 remains unclear. Here, we investigate the effects of PIP2 on Kv2.1 channels by applying exogenous PIP2 to the cytoplasmic face of excised membrane patches, activating muscarinic receptors (M1R), or depleting endogenous PIP2 using a rapamycin-translocated 5-phosphatase (FKBP-Inp54p)...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29369181/revealing-the-action-mechanisms-of-dexamethasone-on-the-birth-weight-of-infant-using-rna-sequencing-data-of-trophoblast-cells
#10
Hongkai Shang, Liping Sun, Thorsten Braun, Qi Si, Jinyi Tong
Dexamethasone (DEX) could induce low birth weight of infant, and low birth weight has close associations with glucocorticoid levels, insulin resistance, hypertension, and metabolic syndrome in adulthood. This study was designed to reveal the action mechanisms of DEX on the birth weight of infant.Using quantitative real-time polymerase chain reaction (qRT-PCR), trophoblast cells of human placenta were identified and the optimum treatment time of DEX were determined. Trophoblast cells were treated by DEX (DEX group) or ethanol (control group) (each group had 3 samples), and then were performed with RNA-sequencing...
January 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29366638/3-4-diaminopyridine-reverses-paralysis-in-botulinum-neurotoxin-intoxicated-diaphragms-through-two-functionally-distinct-mechanisms
#11
Aaron B Bradford, James B Machamer, Trisha M Russo, Patrick M McNutt
Botulinum neurotoxins (BoNTs) are exceedingly potent neurological poisons that prevent neurotransmitter release from peripheral nerve terminals by cleaving presynaptic proteins required for synaptic vesicle fusion. The ensuing neuromuscular paralysis causes death by asphyxiation. Although no antidotal treatments exist to block toxin activity within the nerve terminal, aminopyridine antagonists of voltage-gated potassium channels have been proposed as symptomatic treatments for botulism toxemia. However, clinical evaluation of aminopyridines as symptomatic treatments for botulism has been inconclusive, in part because mechanisms responsible for reversal of paralysis in BoNT-poisoned nerve terminals are not understood...
January 20, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29356177/proline-rich-transmembrane-protein-2-negative-paroxysmal-kinesigenic-dyskinesia-clinical-and-genetic-analyses-of-163-patients
#12
Wo-Tu Tian, Xiao-Jun Huang, Xiao Mao, Qing Liu, Xiao-Li Liu, Sheng Zeng, Xia-Nan Guo, Jun-Yi Shen, Yang-Qi Xu, Hui-Dong Tang, Xiao-Meng Yin, Mei Zhang, Wei-Guo Tang, Xiao-Rong Liu, Bei-Sha Tang, Sheng-Di Chen, Li Cao
BACKGROUND: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. OBJECTIVE: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia. METHODS: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel...
January 22, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29355592/down-regulation-of-inwardly-rectifying-k-currents-in-astrocytes-derived-from-patients-with-monge-s-disease
#13
Wei Wu, Hang Yao, Helen W Zhao, Juan Wang, Gabriel G Haddad
Chronic mountain sickness (CMS) or Monge's disease is a disease in highlanders. These patients have a variety of neurologic symptoms such as migraine, mental fatigue, confusion, dizziness, loss of appetite, memory loss and neuronal degeneration. The cellular and molecular mechanisms underlying CMS neuropathology is not understood. In the previous study, we demonstrated that neurons derived from CMS patients' fibroblasts have a decreased expression and altered gating properties of voltage-gated sodium channel...
January 17, 2018: Neuroscience
https://www.readbyqxmd.com/read/29344180/mir-493-inhibits-proliferation-and-invasion-in-pancreatic-cancer-cells-and-inversely-regulated-herg1-expression
#14
Duo Zhi, Xin Zhao, Mei Dong, Caichuan Yan
The human ether-a-go-go-related potassium channel 1 (hERG1) is a component of the voltage-gated Kv11.1 potassium channel, which has been recently indicated to have a crucial role in the tumorigenesis of multiple tumors, including pancreatic carcinoma. Pancreatic carcinoma is one of the most malignant human cancer types, which has an extremely poor prognosis. The present study demonstrated that the expression levels of hERG1 were markedly elevated in pancreatic cancer tissues and pancreatic cancer cell lines, and that the abnormal hERG1 expression was significantly associated with the proliferation and invasion ability of pancreatic cancer...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29341826/mu-opioid-receptors-inhibit-the-exercise-pressor-reflex-by-closing-n-type-calcium-channels-but-not-by-opening-girk-channels-in-rats
#15
Juan A Estrada, Marc P Kaufman
Mu opioid G-protein coupled receptors (MOR) interact with ion channels to decrease neuronal excitability. In humans, intrathecal administration of the MOR agonist, fentanyl, inhibits the exercise pressor reflex, an effect that can be attributed to either the opening of inward rectifying potassium channels (GIRK) or the closing of N-type calcium channels. The purpose of this study was to determine if the highly selective MOR agonist DAMGO attenuates the exercise pressor reflex, and which of these two channels are responsible for this effect...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29339804/ephb6-and-testosterone-in-concert-regulate-epinephrine-release-by-adrenal-gland-chromaffin-cells
#16
Yujia Wang, Wei Shi, Alexandre Blanchette, Junzheng Peng, Shijie Qi, Hongyu Luo, Jonathan Ledoux, Jiangping Wu
Erythropoietin-producing human hepatocellular receptor (EPH) B6 (EPHB6) is a member of the receptor tyrosine kinase family. We previously demonstrated that EPHB6 knockout reduces catecholamine secretion in male but not female mice, and castration reverses this phenotype. We showed here that male EPHB6 knockout adrenal gland chromaffin cells presented reduced acetylcholine-triggered Ca2+ influx. Such reduction depended on the non-genomic effect of testosterone. Increased large conductance calcium-activated potassium channel current densities were recorded in adrenal gland chromaffin cells from male EPHB6 knockout mice but not from castrated knockout or female knockout mice...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29337221/venom-characterization-of-the-amazonian-scorpion-tityus-metuendus
#17
C V F Batista, J G Martins, R Restano-Cassulini, F I V Coronas, F Z Zamudio, R Procópio, L D Possani
The soluble venom from the scorpion Tityus metuendus was characterized by various methods. In vivo experiments with mice showed that it is lethal. Extended electrophysiological recordings using seven sub-types of human voltage gated sodium channels (hNav1.1 to 1.7) showed that it contains both α- and β-scorpion toxin types. Fingerprint analysis by mass spectrometry identified over 200 distinct molecular mass components. At least 60 sub-fractions were recovered from HPLC separation. Five purified peptides were sequenced by Edman degradation, and their complete primary structures were determined...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29330545/de-novo-bk-channel-variant-causes-epilepsy-by-affecting-voltage-gating-but-not-ca2-sensitivity
#18
Xia Li, Sibylle Poschmann, Qiuyun Chen, Walid Fazeli, Nelly Jouayed Oundjian, Francesca M Snoeijen-Schouwenaars, Oliver Fricke, Erik-Jan Kamsteeg, Marjolein Willemsen, Qing Kenneth Wang
Epilepsy is one of the most common neurological diseases and it causes profound morbidity and mortality. We identified the first de novo variant in KCNMA1 (c.2984 A > G (p.(N995S)))-encoding the BK channel-that causes epilepsy, but not paroxysmal dyskinesia, in two independent families. The c.2984 A > G (p.(N995S)) variant markedly increased the macroscopic potassium current by increasing both the channel open probability and channel open dwell time. The c.2984 A > G (p.(N995S)) variant did not affect the calcium sensitivity of the channel...
January 12, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29321549/probing-the-molecular-basis-of-herg-drug-block-with-unnatural-amino-acids
#19
Logan C Macdonald, Robin Y Kim, Harley T Kurata, David Fedida
Repolarization of the cardiac action potential is primarily mediated by two voltage-dependent potassium currents: I Kr and I Ks . The voltage-gated potassium channel that gives rise to I Kr, Kv11.1 (hERG), is uniquely susceptible to high-affinity block by a wide range of drug classes. Pore residues Tyr652 and Phe656 are critical to potent drug interaction with hERG. It is considered that the molecular basis of this broad-spectrum drug block phenomenon occurs through interactions specific to the aromatic nature of the side chains at Tyr652 and Phe656...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#20
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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