73,850 results match your criteria potassium channel


Therapeutic Antibodies Targeting Potassium Ion Channels.

Handb Exp Pharmacol 2021 May 8. Epub 2021 May 8.

TetraGenetics Inc, Arlington, MA, USA.

Monoclonal antibodies combine specificity and high affinity binding with excellent pharmacokinetic properties and are rapidly being developed for a wide range of drug targets including clinically important potassium ion channels. Nonetheless, while therapeutic antibodies come with great promise, K channels represent particularly difficult targets for biologics development for a variety of reasons that include their dynamic structures and relatively small extracellular loops, their high degree of sequence conservation (leading to immune tolerance), and their generally low-level expression in vivo. The process is made all the more difficult when large numbers of antibody candidates must be screened for a given target, or when lead candidates fail to cross-react with orthologous channels in animal disease models due to their highly selective binding properties. Read More

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Hydrogen sulfide attenuates induction and prevents progress of the 6-hydroxydopamine-induced Parkinsonism in rat through activation of ATP-sensitive potassium channels and suppression of ER stress.

Toxicol Appl Pharmacol 2021 May 4:115558. Epub 2021 May 4.

Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.

Purpose: Studies argue in favor of hydrogen sulfide (HS) as the next potent therapeutic agent for neurodegenerative diseases. In present study, we investigated the effect of long term treatment with NaHS (as donor of HS) on induction and progress of the 6-hydroxydopamine (6-OHDA) -induced Parkinsonism in rat.

Methods: The 6-OHDA was injected into medial forebrain bundle of right hemisphere by stereotaxic surgery. Read More

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A biochemical mechanism for time-encoding memory formation within individual synapses of Purkinje cells.

PLoS One 2021 7;16(5):e0251172. Epub 2021 May 7.

Complexity Science Group, Department of Physics and Astronomy, University of Calgary, Calgary, Alberta, Canada.

Within the classical eye-blink conditioning, Purkinje cells within the cerebellum are known to suppress their tonic firing rates for a well defined time period in response to the conditional stimulus after training. The temporal profile of the drop in tonic firing rate, i.e. Read More

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KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice.

PLoS Genet 2021 May 7;17(5):e1009412. Epub 2021 May 7.

Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

Meiosis is a cell division process with complex chromosome events where various molecules must work in tandem. To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR/Cas9 system and identified potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis. In prophase I, Kctd19 deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of Kctd19 KO mice. Read More

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Utility of red-light ultrafast optogenetic stimulation of the auditory pathway.

EMBO Mol Med 2021 May 7:e13391. Epub 2021 May 7.

Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.

Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in current cochlear implants. Here, we employed fast and very fast variants of the red-light-activated channelrhodopsin (ChR) Chrimson (f-Chrimson and vf-Chrimson) to study their utility for optogenetic stimulation of SGNs in mice. The light requirements were higher for vf-Chrimson than for f-Chrimson, even when optimizing membrane expression of vf-Chrimson by adding potassium channel trafficking sequences. Read More

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KCNK13 potassium channels in the ventral tegmental area of rats are important for excitation of VTA neurons by ethanol.

Alcohol Clin Exp Res 2021 May 7. Epub 2021 May 7.

Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, 60612.

Background: Alcohol excites neurons of the ventral tegmental area (VTA) and the release of dopamine from these neurons is a key event in ethanol reward and reinforcement. Many mechanisms for ethanol actions on neurons of the VTA have been proposed, but antagonists generally do not eliminate ethanol-induced excitation of VTA neurons. We have previously demonstrated that the ion channel KCNK13 plays an important role in ethanol excitation of mouse VTA neurons. Read More

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A novel KCNV2 mutation in a patient taking hydroxychloroquine associated with cone dystrophy with supernormal rod response.

Ophthalmic Genet 2021 May 7:1-6. Epub 2021 May 7.

Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, New York, USA.

: Cone dystrophy with supernormal rod response (CDSRR) is a rare inherited retinal degeneration. A patient superimposed with medical conditions requiring use of hydroxychloroquine (HCQ) may obscure accurate diagnosis of CDSRR. Herein, we report a referral case for HCQ retinopathy screening. Read More

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Large-Conductance Calcium-Activated Potassium Channels and Voltage-Dependent Sodium Channels in Human Cementoblasts.

Front Physiol 2021 20;12:634846. Epub 2021 Apr 20.

Department of Physiology, Tokyo Dental College, Tokyo, Japan.

Cementum, which is excreted by cementoblasts, provides an attachment site for collagen fibers that connect to the alveolar bone and fix the teeth into the alveolar sockets. Transmembrane ionic signaling, associated with ionic transporters, regulate various physiological processes in a wide variety of cells. However, the properties of the signals generated by plasma membrane ionic channels in cementoblasts have not yet been described in detail. Read More

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On Local Activity and Edge of Chaos in a NaMLab Memristor.

Front Neurosci 2021 20;15:651452. Epub 2021 Apr 20.

Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, United States.

Local activity is the capability of a system to amplify infinitesimal fluctuations in energy. Complex phenomena, including the generation of action potentials in neuronal axon membranes, may never emerge in an open system unless some of its constitutive elements operate in a locally active regime. As a result, the recent discovery of solid-state volatile memory devices, which, biased through appropriate DC sources, may enter a local activity domain, and, most importantly, the associated stable yet excitable sub-domain, referred to as edge of chaos, which is where the seed of complexity is actually planted, is of great appeal to the neuromorphic engineering community. Read More

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Gene Set and Pathway Enrichment Analyses Highlight Involvement of Ion Transport in Cholinergic Pathways in Autism: Rationale for Nutritional Intervention.

Front Neurosci 2021 20;15:648410. Epub 2021 Apr 20.

Department of Nutrition and Food Studies, College of Health and Human Services, George Mason University, Fairfax, VA, United States.

Food is the primary human source of choline, an essential precursor to the neurotransmitter acetylcholine, which has a central role in signaling pathways that govern sensorimotor functions. Most Americans do not consume their recommended amount of dietary choline, and populations with neurodevelopmental conditions like autism spectrum disorder (ASD) may be particularly vulnerable to consequences of choline deficiency. This study aimed to identify a relationship between ASD and cholinergic signaling through gene set enrichment analysis and interrogation of existing database evidence to produce a systems biology model. Read More

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The Effect of Amiloride on Proteinuria in Patients with Proteinuric Kidney Disease.

Am J Nephrol 2021 May 6:1-10. Epub 2021 May 6.

Division of Nephrology and Hypertension, Department of Medicine, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.

Introduction: Proteinuric kidney diseases share an aggressive clinical course of developing end-stage renal disease. However, the treatment is limited. Amiloride, an epithelial sodium channel (ENaC) inhibitor, was reported to reduce proteinuria in animal studies and case reports independent of ENaC inhibition. Read More

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Unconventional voltage sensing in an inwardly rectifying potassium channel.

Authors:
Harley T Kurata

J Gen Physiol 2021 Jun 6;153(6). Epub 2021 May 6.

Department of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.

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Structural plasticity of the selectivity filter in a nonselective ion channel.

IUCrJ 2021 May 2;8(Pt 3):421-430. Epub 2021 Apr 2.

Second Target Station, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831, USA.

The sodium potassium ion channel (NaK) is a nonselective ion channel that conducts both sodium and potassium across the cellular membrane. A new crystallographic structure of NaK reveals conformational differences in the residues that make up the selectivity filter between the four subunits that form the ion channel and the inner helix of the ion channel. The crystallographic structure also identifies a side-entry, ion-conduction pathway for Na permeation that is unique to NaK. Read More

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Nicotine Enhances Firing Activity of Layer 5 Pyramidal Neurons in the Medial Prefrontal Cortex through Inhibition of Kv7 Channels.

Biol Pharm Bull 2021 ;44(5):724-731

Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University.

Nicotine enhances attention, working memory and recognition. One of the brain regions associated with these effects of nicotine is the medial prefrontal cortex (mPFC). However, cellular mechanisms that induce the enhancing effects of nicotine remain unclear. Read More

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January 2021

[Electrophysiological Effects of Ionophore-induced Increases in Intracellular Na in Cardiomyocytes].

Yakugaku Zasshi 2021 ;141(5):705-710

Department of Rational Medicinal Science, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.

Na ionophores increase intracellular Na ([Na]i). Membrane potentials and currents were measured using microelectrode and whole-cell patch-clamp techniques. Monensin (10-3×10 M) reduced the slope of the pacemaker potentials and shortened the action potential duration (APD) in sino-atrial nodal and Purkinje cells. Read More

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January 2021

Association of Rare Genetic Variants and Early-Onset Atrial Fibrillation in Ethnic Minority Individuals.

JAMA Cardiol 2021 May 5. Epub 2021 May 5.

Department of Medicine, University of Illinois at Chicago.

Importance: Although rare variants in cardiac ion channels, transcription factors, and myocardial structural proteins are associated with early-onset atrial fibrillation (AF) in White individuals of European descent, it remains unclear whether genetic variation also contributes to the cause of AF in those of minority ethnicity.

Objectives: To assess the prevalence of rare and novel pathogenic variants in candidate genes in ethnic minority probands with early-onset AF and determine genotype-phenotype associations.

Design, Setting, And Participants: In this cohort, family-based study, probands of African and Hispanic descent with early-onset AF (defined as AF occurring in individuals aged ≤66 years) prospectively enrolled in a clinical and genetic biorepository underwent sequencing of 60 candidate genes. Read More

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Cilostazol eliminates radiation-resistant glioblastoma by re-evoking big conductance calcium-activated potassium channel activity.

Am J Cancer Res 2021 15;11(4):1148-1169. Epub 2021 Apr 15.

Institute of Basic Medical Sciences, National Cheng Kung University Hospital Taiwan.

In spite of radio- and chemotherapy, glioblastoma (GBM) develops therapeutic resistance leading to recurrence and poor prognosis. Therefore, understanding the underlying mechanisms of resistance is important to improve the treatment of GBM. To this end, we developed a radiation-resistant cell model by exposure to consecutive periods of irradiation. Read More

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Overcoming challenges of HERG potassium channel liability through rational design: Eag1 inhibitors for cancer treatment.

Med Res Rev 2021 May 4. Epub 2021 May 4.

AG Oncophysiology, Max-Planck Institute for Experimental Medicine, Göttingen, Germany.

Two decades of research have proven the relevance of ion channel expression for tumor progression in virtually every indication, and it has become clear that inhibition of specific ion channels will eventually become part of the oncology therapeutic arsenal. However, ion channels play relevant roles in all aspects of physiology, and specificity for the tumor tissue remains a challenge to avoid undesired effects. Eag1 (K 10. Read More

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Calcium-Activated K Channels (KCa) and Therapeutic Implications.

Handb Exp Pharmacol 2021 May 5. Epub 2021 May 5.

Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland.

Potassium channels are the most diverse and ubiquitous family of ion channels found in cells. The Ca and voltage gated members form a subfamily that play a variety of roles in both excitable and non-excitable cells and are further classified on the basis of their single channel conductance to form the small conductance (SK), intermediate conductance (IK) and big conductance (BK) K channels.In this chapter, we will focus on the mechanisms underlying the gating of BK channels, whose function is modified in different tissues by different splice variants as well as the expanding array of regulatory accessory subunits including β, γ and LINGO subunits. Read More

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Genome-wide DNA methylation analysis and biochemical responses provide insights into the initial domestication of halophyte Puccinellia tenuiflora.

Plant Cell Rep 2021 May 4. Epub 2021 May 4.

Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun, 130024, China.

Key Message: Puccinellia tenuiflora was domesticated for two years by growing it under non-saline conditions, providing epigenetic and biochemical insights into the initial domestication of extreme halophytes. Some halophytes have economic value as crop species. The domestication of halophytes may offer hope in solving the problem of soil salinization. Read More

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High renin hypertension in focal renal fibromuscular dysplasia: turn off of renin system angiotensin overactivation by renal angioplasty cured high blood pressure and quickly reversed myocardial hypertrophy.

Acta Biomed 2021 Apr 30;92(S1):e2021162. Epub 2021 Apr 30.

University of Parma.

Background Fibromuscolar dysplasia (FMD) is an idiopathic, non-atherosclerotic and non-inflammatory stenotic lesion of renal arteries causing renovascular hypertension up-regulating renin-angiotensin-aldosterone system. Case report: A 18-year-old man was referred to our Hypertension Center (Clinica e Terapia Medica) for the recent onset of hypertension, poorly controlled on calcium channel blockers, already associated to electrocardiographic and echocardiography signs of left ventricular hypertrophy and significant albuminuria (728 mg/24 h). An increased plasma renin activity (PRA), aldosterone level and a mild hypokalemia raised the suspicion of renovascular hypertension. Read More

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Hyperammonemia in Patients With Status Epilepticus Treated With or Without Valproic Acid.

Neurologist 2021 May 5;26(3):80-82. Epub 2021 May 5.

Department of Neurology, Mayo Clinic, Rochester, MN.

Background: Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA.

Methods: Charts of adult patients with SE from St. Read More

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Antiarrhythmic Hit to Lead Refinement in a Dish Using Patient-Derived iPSC Cardiomyocytes.

J Med Chem 2021 May 4. Epub 2021 May 4.

Cardiovascular Institute and Department of Medicine, Stanford University, Stanford, California 94305, United States.

Ventricular cardiac arrhythmia (VA) arises in acquired or congenital heart disease. Long QT syndrome type-3 (LQT3) is a congenital form of VA caused by cardiac sodium channel (I) SCN5A mutations that prolongs cardiac action potential (AP) and enhances I current. Mexiletine inhibits I and shortens the QT interval in LQT3 patients. Read More

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A Phase 1 Study to Investigate the Effects of Cortexolone 17α-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity.

Clin Pharmacol Drug Dev 2021 May 3. Epub 2021 May 3.

St George's, University of London, London, United Kingdom.

Cortexolone 17α-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17α-propionate was found to have a weak inhibitory effect on human Ether-à-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17α-propionate is absorbed. Read More

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Rapid volume pulsation of the extracellular space coincides with epileptiform activity in mice and depends on the NBCe1 transporter.

J Physiol 2021 May 3. Epub 2021 May 3.

Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.

Key Points: Extracellular space (ECS) rapid volume pulsation (RVP) accompanying epileptiform activity is described for the first time. Such RVP occurs robustly in several in vitro and in vivo mouse models of epileptiform activity. In the in vitro 4-aminopyridine model of epileptiform activity, RVP depends on the activity of the electrogenic Na /HCO cotransporter (NBCe1). Read More

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Morvan syndrome associated with LGI1 antibody: a case report.

BMC Neurol 2021 May 3;21(1):185. Epub 2021 May 3.

Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.

Background: Morvan syndrome (MoS) is a rare autoimmune syndrome associated with antibodies against two kinds of potassium channel proteins, contactin associated protein-like 2 (CASPR2) and leucine-rich glioma inactivated protein 1 (LGI1). MoS patients with only LGI1-antibody seropositivity have rarely been reported. Here, we describe a 64-year-old male MoS patient with only LGI1-antibody seropositivity. Read More

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Informing NMR experiments with molecular dynamics simulations to characterize the dominant activated state of the KcsA ion channel.

J Chem Phys 2021 Apr;154(16):165102

Department of Chemistry, Columbia University, New York, New York 10027, USA.

As the first potassium channel with an x-ray structure determined, and given its homology to eukaryotic channels, the pH-gated prokaryotic channel KcsA has been extensively studied. Nevertheless, questions related, in particular, to the allosteric coupling between its gates remain open. The many currently available x-ray crystallography structures appear to correspond to various stages of activation and inactivation, offering insights into the molecular basis of these mechanisms. Read More

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Kcns3 deficiency disrupts Parvalbumin neuron physiology in mouse prefrontal cortex: Implications for the pathophysiology of schizophrenia.

Neurobiol Dis 2021 Apr 30:105382. Epub 2021 Apr 30.

Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address:

The unique fast spiking (FS) phenotype of cortical parvalbumin-positive (PV) neurons depends on the expression of multiple subtypes of voltage-gated potassium channels (Kv). PV neurons selectively express Kcns3, the gene encoding Kv9.3 subunits, suggesting that Kcns3 expression is critical for the FS phenotype. Read More

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Activation of the kidney sodium chloride cotransporter by the β2-adrenergic receptor agonist salbutamol increases blood pressure.

Kidney Int 2021 Apr 30. Epub 2021 Apr 30.

Department of Biomedicine, Aarhus University, Aarhus DK-8000, Denmark. Electronic address:

The thiazide-sensitive sodium-chloride-cotransporter (NCC) in the kidney distal convoluted tubule (DCT) plays an essential role in sodium and potassium homeostasis. Here, we demonstrate that NCC activity is increased by the β2-adrenoceptor agonist salbutamol, a drug prevalently used to treat asthma. Relative to β1-adrenergic receptors, the β2-adrenergic receptors were greatly enriched in mouse DCT cells. Read More

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Identification of PUFA interaction sites on the cardiac potassium channel KCNQ1.

J Gen Physiol 2021 Jun 3;153(6). Epub 2021 May 3.

Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Polyunsaturated fatty acids (PUFAs), but not saturated fatty acids, modulate ion channels such as the cardiac KCNQ1 channel, although the mechanism is not completely understood. Using both simulations and experiments, we find that PUFAs interact directly with the KCNQ1 channel via two different binding sites: one at the voltage sensor and one at the pore. These two amphiphilic binding pockets stabilize the negatively charged PUFA head group by electrostatic interactions with R218, R221, and K316, while the hydrophobic PUFA tail is selectively stabilized by cassettes of hydrophobic residues. Read More

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