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Potassium current voltage clamp

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https://www.readbyqxmd.com/read/29778719/effect-of-heptanol-and-ethanol-on-excitation-wave-propagation-in-a-neonatal-rat-ventricular-myocyte-monolayer
#1
A D Podgurskaya, V A Tsvelaya, S R Frolova, I Y Kalita, N N Kudryashova, K I Agladze
In this work, the action of heptanol and ethanol was investigated in a two-dimensional (2D) model of cardiac tissue: the neonatal rat ventricular myocyte monolayer. Heptanol is known in electrophysiology as a gap junction uncoupler but may also inhibit voltage-gated ionic channels. Ethanol is often associated with the occurrence of arrhythmias. These substances influence sodium, calcium, and potassium channels, but the complete mechanism of action of heptanol and ethanol remains unknown. The optical mapping method was used to measure conduction velocities (CVs) in concentrations of 0...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29769222/transient-outward-k-current-i-to-underlies-the-right-ventricular-initiation-of-polymorphic-ventricular-tachycardia-in-a-transgenic-rabbit-model-of-long-qt-syndrome-type-1
#2
Bum-Rak Choi, Weiyan Li, Dmitry Terentyev, Anatoli Y Kabakov, Mingwang Zhong, Colin M Rees, Radmila Terentyeva, Tae Yun Kim, Zhilin Qu, Xuwen Peng, Alain Karma, Gideon Koren
BACKGROUND: Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1. METHODS: Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits...
June 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29753045/identification-and-functional-characterization-of-zebrafish-k-2p-17-1-task-4-talk-2-two-pore-domain-k-channels
#3
Ingo Staudacher, Claudius Illg, Jakob Gierten, Sebastian Seehausen, Patrick A Schweizer, Hugo A Katus, Dierk Thomas
Human K2P 17.1 (TASK-4, TALK-2) two-pore-domain potassium (K2P ) channels have recently been implicated in heart rhythm disorders including atrial fibrillation and conduction disease. The functional in vivo significance of K2P 17.1 currents in cardiac electrophysiology remains incompletely understood. Danio rerio (zebrafish) may be utilized to elucidate the role of cardiac K2P channels in vivo. The aim of this work was to identify and characterize the zebrafish ortholog of K2P 17.1 in comparison to its human counterpart...
May 9, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29746171/increased-task-channel-mediated-currents-underlie-high-fat-diet-induced-vagal-afferent-dysfunction
#4
Sung Jin Park, Yang Yu, Brittany Wagner, William C Valinsky, Alan E Lomax, Michael J Beyak
We have previously demonstrated that satiety sensing vagal afferent neurons are less responsive to meal-related stimuli in obesity, due to reduced electrical excitability. As leak K+ currents are key determinants of membrane excitability, we hypothesized that leak K+ currents are increased in vagal afferents during obesity. Diet-induced obesity (DIO) was induced by feeding C57Bl/6J mice a high fat fed diet (60% energy from fat - HFF) for 8-10 weeks. In vitro extracellular recordings were performed on jejunal afferent nerves...
May 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29717493/mir-1-is-increased-in-pulmonary-hypertension-and-downregulates-kv1-5-channels-in-rat-pulmonary-arteries
#5
Gema Mondejar-Parreño, María Callejo, Bianca Barreira, Daniel Morales-Cano, Sergio Esquivel-Ruiz, Laura Moreno, Angel Cogolludo, Francisco Perez-Vizcaino
KEY POINTS: ■The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. ■PASMC from this animal model are more depolarised and show decreased expression and activity of Kv1.5. ■miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. ■Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. ABSTRACT: Impairment of voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH)...
May 2, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29705539/kir-4-1-inward-rectifier-potassium-channel-is-upregulated-in-astrocytes-in-a-murine-multiple-sclerosis-model
#6
Francisco Mercado, Angélica Almanza, Nazario Rubio, Enrique Soto
Multiple sclerosis (MS) is a high prevalence degenerative disease characterized at the cellular level by glial and neuronal cell death. The causes of cell death during the disease course are not fully understood. In this work we demonstrate that in a MS model induced by Theiler's murine encephalomyelitis virus (TMEV) infection, the inward rectifier (Kir) 4.1 potassium channel subunit is overexpressed in astrocytes. In voltage clamp experiments the inward current density from TMEV-infected astrocytes was significantly larger than in mock-infected ones...
April 26, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29665277/the-expression-of-endogenous-voltage-gated-potassium-channels-in-hek293-cells-is-affected-by-culture-conditions
#7
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/29643254/new-targets-for-old-drugs-cardiac-glycosides-inhibit-atrial-specific-k2p3-1-task-1-channels
#8
Constanze Schmidt, Felix Wiedmann, Anne-Rike Gaubatz, Antonius Ratte, Hugo A Katus, Dierk Thomas
Cardiac glycosides have been used in the treatment of arrhythmias for more than 200 years. Two-pore-domain (K2P) potassium channels regulate cardiac action potential repolarization. Recently, K2P3.1 (TASK-1) has been implicated in atrial fibrillation (AF) pathophysiology and was suggested as atrial-selective antiarrhythmic drug target. We hypothesized that blockade of cardiac K2P channels contributes to the mechanism of action of digitoxin and digoxin. All functional human K2P channels were screened for interactions with cardiac glycosides...
April 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29617054/activation-of-voltage-gated-sodium-current-and-inhibition-of-erg-mediated-potassium-current-caused-by-telmisartan-an-antagonist-of-angiotensin-ii-type-1-receptor-in-hl-1-atrial-cardiomyocytes
#9
Wei-Ting Chang, Sheng-Nan Wu
Telmisartan (TEL) is a non-peptide blocker of angiotensin II type-1 (AT1 ) receptor. However, the mechanisms through which this drug interacts directly with ion currents in hearts remain largely unclear. Herein, we aim to investigate the effects of TEL the on ionic currents and membrane potential of murine HL-1 cardiomyocytes. In whole-cell recordings, addition of TEL stimulated the peak and late components of voltage-gated Na+ currents (IN a ) with different potencies. The EC50 values required to achieve the stimulatory effect of this drug on peak and late IN a were 0...
April 4, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29599640/the-effects-of-4-hydroxybenzoic-acid-identified-from-bamboo-dendrocalamus-asper-shoots-on-kv1-4-channel
#10
Jingli Zhang, Fatin H Mohamad, Jia Hui Wong, Habsah Mohamad, Abdul Hadi Ismail, Abdul Aziz Mohamed Yusoff, Hasnah Osman, Kok Tong Wong, Zamzuri Idris, Jafri Malin Abdullah
Background: Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating Shaker -related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type...
February 2018: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/29593552/k-v-4-3-expression-modulates-na-v-1-5-sodium-current
#11
Vincent Portero, Ronald Wilders, Simona Casini, Flavien Charpentier, Arie O Verkerk, Carol Ann Remme
In cardiomyocytes, the voltage-gated transient outward potassium current (Ito ) is responsible for the phase-1 repolarization of the action potential (AP). Gain-of-function mutations in KCND3 , the gene encoding the Ito carrying KV 4.3 channel, have been associated with Brugada syndrome (BrS). While the role of Ito in the pro-arrhythmic mechanism of BrS has been debated, recent studies have suggested that an increased Ito may directly affect cardiac conduction. However, the effects of an increased Ito on AP upstroke velocity or sodium current at the cellular level remain unknown...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29574723/calcium-dependent-potassium-channels-control-proliferation-of-cardiac-progenitor-cells-and-bone-marrow-derived-mesenchymal-stem-cells
#12
Patrick Vigneault, Patrice Naud, Xiaoyan Qi, Jiening Xiao, Louis Villeneuve, Darryl R Davis, Stanley Nattel
Endogenous c-Kit+ cardiac progenitor cells (eCPCs) and bone marrow (BM)-derived mesenchymal stem cells (MSCs) are being developed for cardiac regenerative therapy, but a better understanding of their physiology is needed. Here, we addressed the unknown functional role of ion-channels in freshly-isolated eCPCs and expanded BM-MSCs using patch-clamp, microfluorometry and confocal microscopy. Isolated c-Kit+ eCPCs were purified from dog hearts by immunomagnetic selection. Ion-currents were barely detectable in freshly-isolated c-Kit+ eCPCs with intracellular calcium (Ca2+ i ) buffered...
March 25, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29573276/sinusoidal-voltage-protocols-for-rapid-characterisation-of-ion-channel-kinetics
#13
Kylie A Beattie, Adam P Hill, Rémi Bardenet, Yi Cui, Jamie I Vandenberg, David J Gavaghan, Teun P de Boer, Gary R Mirams
Understanding the roles of ion currents is crucial to predict the action of pharmaceuticals and mutations in different scenarios, and thereby to guide clinical interventions in the heart, brain and other electrophysiological systems. Our ability to predict how ion currents contribute to cellular electrophysiology is in turn critically dependent on our characterisation of ion channel kinetics - the voltage-dependent rates of transition between open, closed and inactivated channel states. We present a new method for rapidly exploring and characterising ion channel kinetics, applying it to the hERG potassium channel as an example, with the aim of generating a quantitatively predictive representation of the ion current...
March 24, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29572918/status-epilepticus-role-for-etiology-in-determining-response-to-benzodiazepines
#14
Suchitra Joshi, Karthik Rajasekaran, Kyle M Hawk, Stephen J Chester, Howard P Goodkin
OBJECTIVE: Clinical factors contributing to benzodiazepine failure in treating status epilepticus include suboptimal dosing and seizure duration. As many benzodiazepine-refractory episodes of status epilepticus (SE) arise from acute etiologies, we sought to determine whether etiology impacts SE treatment. METHODS: The potency of diazepam to terminate SE induced by lithium-pilocarpine (LiPilo-SE) or kainic acid (KA-SE) in 3-week old rats was studied by video-electroencephalograpy...
March 24, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29567111/direct-evidence-of-impaired-neuronal-na-k-atpase-pump-function-in-alternating-hemiplegia-of-childhood
#15
Christine Q Simmons, Christopher H Thompson, Bryan E Cawthon, Grant Westlake, Kathryn J Swoboda, Evangelos Kiskinis, Kevin C Ess, Alfred L George
Mutations in ATP1A3 encoding the catalytic subunit of the Na/K-ATPase expressed in mammalian neurons cause alternating hemiplegia of childhood (AHC) as well as an expanding spectrum of other neurodevelopmental syndromes and neurological phenotypes. Most AHC cases are explained by de novo heterozygous ATP1A3 mutations, but the fundamental molecular and cellular consequences of these mutations in human neurons are not known. In this study, we investigated the electrophysiological properties of neurons generated from AHC patient-specific induced pluripotent stem cells (iPSCs) to ascertain functional disturbances underlying this neurological disease...
March 19, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29566261/effects-of-trimethoprim-sulfadiazine-and-detomidine-on-the-function-of-equine-k-v-11-1-channels-in-a-two-electrode-voltage-clamp-tevc-oocyte-model
#16
D S Trachsel, M A Tejada, V Groesfjeld Christensen, P J Pedersen, J K Kanters, R Buhl, K Calloe, D A Klaerke
The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction between drugs and potassium channels, especially the Kv 11.1 channel. Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine. However, some compounds, such as trimethoprim-sulfonamide combinations are still widely used in veterinarian medicine. Therefore, we investigate the effect of trimethoprim-sulfadiazine (TMS), trimethoprim, sulfadiazine, and detomidine on equine-specific Kv 11...
March 22, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29561202/the-inward-rectifier-potassium-current-i-kir-promotes-the-intrinsic-pacemaker-activity-of-thalamocortical-neurons
#17
Yimy Amarillo, Angela Isabel Tissone, German Mato, Marcela S Nadal
Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (< 4 Hz), which are the physiological oscillations during N-REM sleep, or pathological ones during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that up-regulation of the small and neglected inward rectifier potassium current IKir induces repetitive burst firing at slow and delta frequency bands...
March 21, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29486387/modulation-of-calcium-and-potassium-permeation-in-plant-tpc-channels
#18
Armando Carpaneto, Antonella Gradogna
Plant two-pore channels (TPCs) are non-selective cation channels permeable both to monovalent potassium and divalent calcium. We previously developed a technique that allowed the simultaneous determination of the fluxes of these two ions across the channel by a combined use of patch-clamp and fluorescence. In this paper we studied how potassium and calcium fluxes were influenced by modification of cytosolic concentrations of K+ and Ca2+ . A decrease in cytosolic calcium from 2 to 0.5 mM led to a shift of the activation curve of about +60 mV; although at positive potentials currents were very similar, calcium ion permeation was significantly reduced and the ratio between the total and calcium-mediated current increased about two-fold...
May 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29483285/heteromeric-k-v-2-k-v-8-2-channels-mediate-delayed-rectifier-potassium-currents-in-primate-photoreceptors
#19
Jacqueline Gayet-Primo, Daniel B Yaeger, Roupen A Khanjian, Teresa Puthussery
Silent voltage-gated potassium channel subunits (KV S) interact selectively with members of the KV 2 channel family to modify their functional properties. The localization and functional roles of these silent subunits remain poorly understood. Mutations in the KV S subunit, KV 8.2 ( KCNV2 ), lead to severe visual impairment in humans, but the basis of these deficits remains unclear. Here, we examined the localization, native interactions, and functional properties of KV 8.2-containing channels in mouse, macaque, and human photoreceptors of either sex...
April 4, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29479853/zinc-oxide-nanoparticles-and-voltage-gated-human-k-v-11-1-potassium-channels-interact-through-a-novel-mechanism
#20
Stefania Piscopo, Euan R Brown
Membrane-nanoparticle interactions are important in determining the effects of manufactured nanomaterials on cell physiology and pathology. Here, silica, titanium, zinc, and magnesium oxide nanoparticles are screened against human hERG (Kv 11.1) voltage-gated potassium channels under a whole-cell voltage clamp. 10 µg mL-1 ZnO uniquely increases the amplitude of the steady-state current, decreases the rate of hERG current inactivation during steady-state depolarization, accelerates channel deactivation during resurgent tail currents, and shows no significant alteration of current activation rate or voltage dependence...
April 2018: Small
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