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Late sodium current

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https://www.readbyqxmd.com/read/29362862/the-development-of-an-in-vitro-pig-a-assay-in-l5178y-cells
#1
Rhiannon David, Emily Talbot, Bethany Allen, Amy Wilson, Usman Arshad, Ann Doherty
A recent flow cytometry-based in vivo mutagenicity assay involves the hemizygous phosphatidylinositol class A (Pig-a) gene. Pig-a forms the catalytic subunit of N-acetylglucosaminyltransferase required for glycophosphatidylinositol (GPI) anchor biosynthesis. Mutations in Pig-a prevent GPI-anchor synthesis resulting in loss of cell-surface GPI-linked proteins. The aim of the current study was to develop and validate an in vitro Pig-a assay in L5178Y mouse lymphoma cells. Ethyl methanesulfonate (EMS)-treated cells (186...
January 23, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29357519/enhanced-basal-late-sodium-current-appears-to-underlie-the-age-related-prolongation-of-action-potential-duration-in-guinea-pig-ventricular-myocytes
#2
Yejia Song, Luiz Belardinelli
Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na+ current (INaL); 3) inhibition of INaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H2O2). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs)...
December 14, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29321131/efficacy-of-ranolazine-in-patients-with-symptomatic-hypertrophic-cardiomyopathy-the-restyle-hcm-randomized-double-blind-placebo-controlled-study
#3
Iacopo Olivotto, Paolo G Camici, Piera Angelica Merlini, Claudio Rapezzi, Monica Patten, Vicent Climent, Gianfranco Sinagra, Benedetta Tomberli, Francisco Marin, Philipp Ehlermann, Lars S Maier, Alessandra Fornaro, Claudius Jacobshagen, Antonello Ganau, Luciano Moretti, Antonio Hernandez Madrid, Raffaele Coppini, Giorgio Reggiardo, Corrado Poggesi, Francesco Fattirolli, Luiz Belardinelli, Gianfranco Gensini, Alessandro Mugelli
BACKGROUND: The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. METHODS AND RESULTS: In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months...
January 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29285947/eslicarbazepine-acetate-in-epilepsies-with-focal-and-secondary-generalised-seizures-systematic-review-of-current-evidence
#4
Laurent M Willems, Johann Philipp Zöllner, Esther Paule, Susanne Schubert-Bast, Felix Rosenow, Adam Strzelczyk
Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved for adjunctive treatment in adults, children, and adolescents with focal-onset seizures. Recently ESL was approved for initial monotherapy in adults. The intention of this article is to review current evidence for ESL and to summarise its pharmacological profile in comparison to other AEDs of the dibenzazepine group. Areas covered: We performed a systematic literature search in electronic databases (MEDLINE database, Cochrane Central Register of Controlled Trials, Excerpta Medica dataBASE) using a combined search strategy including the following keywords: eslicarbazepine, epilepsy and seizure...
December 29, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29243206/ical-and-ito-mediate-rate-dependent-repolarization-in-rabbit-atrial-myocytes
#5
Jian-Wen Hou, Wei Li, Yu-Dong Fei, Yi-He Chen, Qian Wang, Yue-Peng Wang, Yi-Gang Li
Rate-dependent repolarization (RDR) of action potential (AP) in cardiomyocyte plays a critical role in the genesis of arrhythmias and RDR in atrium has been linked with atrial fibrillation. However, detailed studies focusing on the role of RDR in rabbit atrium are scant. In this study, atrial cells were isolated from rabbit heart and rate-dependent property was explored in single atrial cell to elucidate the underlying mechanism. Our results indicated that rate-dependent prolongation was evident at the action potential duration at 20% (APD20) and 50% (APD50) repolarization but not at 90% repolarization (APD90) under control condition...
December 14, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29222390/sodium-channel-remodeling-in-subcellular-microdomains-of-murine-failing-cardiomyocytes
#6
Mathilde R Rivaud, Esperanza Agullo-Pascual, Xianming Lin, Alejandra Leo-Macias, Mingliang Zhang, Eli Rothenberg, Connie R Bezzina, Mario Delmar, Carol Ann Remme
BACKGROUND: Cardiac sodium channel (NaV1.5) dysfunction contributes to arrhythmogenesis during pathophysiological conditions. Nav1.5 localizes to distinct subcellular microdomains within the cardiomyocyte, where it associates with region-specific proteins, yielding complexes whose function is location specific. We herein investigated sodium channel remodeling within distinct cardiomyocyte microdomains during heart failure. METHODS AND RESULTS: Mice were subjected to 6 weeks of transverse aortic constriction (TAC; n=32) to induce heart failure...
December 8, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29193076/resurgent-sodium-current-promotes-action-potential-firing-in-the-avian-auditory-brainstem
#7
Hui Hong, Ting Lu, Xiaoyu Wang, Yuan Wang, Jason Tait Sanchez
Auditory brainstem neurons are functionally primed to fire action potentials (APs) at markedly high-rates in order to rapidly encode acoustic information of sound. This specialization is critical for survival and the comprehension of behaviourally relevant communication functions, including sound localization and understanding speech in noise. Here, we investigated underlying ion channel mechanisms essential for high-rate AP firing in neurons of the chicken nucleus magnocellularis (NM) - the avian analog of bushy cells of the mammalian anteroventral cochlear nucleus...
November 28, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29177922/sglt1-and-sglt1-inhibitors-a-role-to-be-assessed-in-the-current-clinical-practice
#8
Leonardo Spatola, Silvia Finazzi, Claudio Angelini, Marco Dauriz, Salvatore Badalamenti
Diabetes is a complex disease of increasingly common occurrence worldwide. Attaining optimal glycemic control is the main challenge to prevent the development of diabetes-related complications and/or to stop their progression. In recent years, the pharmacologic toolkit for the treatment of diabetes has considerably expanded, thus paving the way to more pathophysiology-oriented therapies. For instance, the sodium-glucose cotransporters SGLT2 and SGLT1 have been in the spotlight because of better knowledge of their physiology and therapeutic potential...
November 24, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29139614/human-dental-stem-cell-derived-transgene-free-ipscs-generate-functional-neurons-via-embryoid-body-mediated-and-direct-induction-methods
#9
Ikbale El Ayachi, Jun Zhang, Xiao-Ying Zou, Zongdong Yu, Wei Wei, Kristen M S O'Connell, George T-J Huang
Induced pluripotent stem cells (iPSCs) give rise to neural stem/progenitor cells (NSCs), serving as a good source for neural regeneration. Here, we established transgene-free (TF) iPSCs from dental stem cells (DSCs) and determined their capacity to differentiate into functional neurons in vitro. Generated TF iPSCs from stem cells of apical papilla (SCAP) and dental pulp stem cells (DPSCs) underwent two methods -- embryoid body (EB)-mediated and direct induction, to guide TF-DSC iPSCs along with H9 or H9 Syn-GFP (human embryonic stem cells) into functional neurons in vitro...
November 15, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29130489/angiotensin-1-7-modulates-electrophysiological-characteristics-and-calcium-homeostasis-in-pulmonary-veins-cardiomyocytes-via-mas-pi3k-enos-signaling-pathway
#10
Yen-Yu Lu, Wen-Shiann Wu, Yung-Kuo Lin, Chen-Chuan Cheng, Yao-Chang Chen, Shih-Ann Chen, Yi-Jen Chen
BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia, and pulmonary veins (PVs) play a critical role in triggering AF. Angiotensin (Ang)-(1-7) regulates calcium (Ca(2+) ) homeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang-(1-7) in PV arrhythmogenesis remains unclear. MATERIALS AND METHODS: Conventional microelectrodes, whole-cell patch-clamp, and the Fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca(2+) in isolated rabbit PV preparations, and in single isolated PV cardiomyocytes, before and after administration of Ang-(1-7)...
November 12, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29127493/late-sodium-current-associated-cardiac-electrophysiological-and-mechanical-dysfunction
#11
REVIEW
Shandong Yu, Gang Li, Christopher L-H Huang, Ming Lei, Lin Wu
Late sodium current (INaL) is a small sustained inward current observed during the cardiac action potential plateau phase following decay of the early peak INa. The endogenous INaL is relatively small in normal hearts but exerts functionally significant effects on cardiomyocyte repolarization with potentially pro-arrhythmic effects in hearts with reduced repolarization reserve. Enhanced INa,L occurs in long QT syndrome 3 (LQTS 3) patients, and under a number of pathological and pharmacological cardiovascular conditions, including bradycardia, myocardial ischemia, reperfusion injury, and heart failure...
November 10, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29072259/barbaloin-inhibits-ventricular-arrhythmias-in-rabbits-by-modulating-voltage-gated-ion-channels
#12
Zhen-Zhen Cao, You-Jia Tian, Jie Hao, Pei-Hua Zhang, Zhi-Pei Liu, Wan-Zhen Jiang, Meng-Liu Zeng, Pei-Pei Zhang, Ji-Hua Ma
Barbaloin (10-β-D-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)-anthracenone) is extracted from the aloe plant and has been reported to have anti-inflammatory, antitumor, antibacterial, and other biological activities. Here, we investigated the effects of barbaloin on cardiac electrophysiology, which has not been reported thus far. Cardiac action potentials (APs) and ionic currents were recorded in isolated rabbit ventricular myocytes using whole-cell patch-clamp technique. Additionally, the antiarrhythmic effect of barbaloin was examined in Langendorff-perfused rabbit hearts...
October 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28972668/wenxin-keli-diminishes-ca2-overload-induced-by-hypoxia-reoxygenation-in-cardiomyocytes-through-inhibiting-inal-and-ical
#13
Antao Luo, Zhipei Liu, Zhenzhen Cao, Jie Hao, Lin Wu, Chen Fu, Mengliu Zeng, Wanzhen Jiang, Peihua Zhang, Buchang Zhao, Tao Zhao, Jing Zhao, Jihua Ma
BACKGROUND: An increase in the late sodium current (INaL ) causes intracellular Na+ overload and subsequently intracellular Ca2+ ([Ca2+ ]i ) overload via the stimulated reverse Na+ -Ca2+ exchange (NCX). Wenxin Keli (WXKL) is an effective antiarrhythmic Chinese herb extract, but the underlying mechanisms are unclear. METHODS AND RESULTS: The INaL , NCX current (INCX ), L-type Ca2+ current (ICaL ), and action potentials were recorded using the whole-cell patch-clamp technique in rabbit ventricular myocytes...
December 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28971840/selective-inhibition-of-physiological-late-sodium-current-stabilizes-ventricular-repolarization
#14
Nesrine El-Bizri, Cindy Hong Li, Gong-Xin Liu, Sridharan Rajamani, Luiz Belardinelli
BACKGROUND: The physiological role of cardiac late Na+ current (INa) has not been well described. In this study, we tested the hypothesis that selective inhibition of physiological late INa abbreviates the normal action potential duration (APD) and counteracts the prolongation of APD and arrhythmic activities caused by inhibition of delayed rectifier K+ current, IKr. METHODS: The effects of GS-458967 (GS967) on the physiological late INa and action potentials (APs) in rabbit isolated ventricular myocytes and on the monophasic APs (MAPs) and arrhythmias in rabbit isolated perfused hearts were determined...
September 29, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28951728/urinary-exosomes-and-their-cargo-potential-biomarkers-for-mineralocorticoid-arterial-hypertension
#15
REVIEW
Eric R Barros, Cristian A Carvajal
Arterial hypertension (AHT) currently affects approximately 40% of adults worldwide, and its pathological mechanisms are mainly related to renal, vascular, and endocrine systems. Steroid hormones as aldosterone and cortisol are highly relevant to human endocrine physiology, and also to endocrine hypertension. Pathophysiological conditions, such as primary aldosteronism, affect approximately 10% of patients diagnosed with AHT and are secondary to a high production of aldosterone, increasing the risk also for cardiovascular damage and heart diseases...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28928044/electrocardiographic-biomarkers-to-confirm-drug-s-electrophysiological-effects-used-for-proarrhythmic-risk-prediction-under-cipa
#16
Jose Vicente, Meisam Hosseini, Lars Johannesen, David G Strauss
The ECG plays a critical role in the thorough QT study. This clinical study is part of the assessment of proarrhythmic potential of drugs under the current regulatory paradigm. While the current paradigm has been successful in preventing drugs with unexpected QT prolongation or torsade risk from reaching the market, the focus on QT prolongation has likely resulted in potentially beneficial compounds with minimal torsade risk being dropped from development. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a new mechanistic-based paradigm for cardiac safety evaluation of drugs...
August 9, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28924617/dynamics-of-sodium-current-mediated-early-afterdepolarizations
#17
Daisuke Sato, Colleen E Clancy, Donald M Bers
Early afterdepolarizations (EADs) have been attributed to two primary mechanisms: 1) recovery from inactivation of the L-type calcium (Ca) channel and/or 2) spontaneous Ca release, which depolarizes the membrane potential through the electrogenic sodium-calcium exchanger (NCX). The sodium (Na) current (INa), especially the late component of the Na current, has been recognized as an important player to set up the conditions for EADs by reducing repolarization reserve and increasing intracellular Na concentration, which leads to Ca overload...
September 2017: Heliyon
https://www.readbyqxmd.com/read/28913981/age-dependent-expression-of-nav1-9-channels-in-medial-prefrontal-cortex-pyramidal-neurons-in-rats
#18
Maciej Gawlak, Bartłomiej Szulczyk, Adam Berłowski, Katarzyna Grzelka, Anna Stachurska, Justyna Pełka, Katarzyna Czarzasta, Maciej Małecki, Przemysław Kurowski, Ewa Nurowska, Paweł Szulczyk
Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na(+) current that is TTX resistant with a low threshold and noninactivating over time. The purpose of this study was to assess the presence of Nav1.9 channels in medial prefrontal cortex (mPFC) layer II and V pyramidal neurons in young (20-day old), late adolescent (60-day old), and adult (6- to 7-month old) rats...
December 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28867216/the-effect-of-phosphorylation-on-the-salt-tolerance-related-functions-of-the-soybean-protein-pm18-a-member-of-the-group-3-lea-protein-family
#19
Yun Liu, Meiyan Yang, Hua Cheng, Nan Sun, Simu Liu, Shuiming Li, Yong Wang, Yizhi Zheng, Vladimir N Uversky
Enzymatically driven post-translated modifications (PTMs) usually happen within the intrinsically disordered regions of a target protein and can modulate variety of protein functions. Late embryogenesis abundant (LEA) proteins are a family of the plant intrinsically disordered proteins (IDPs). Despite their important roles in plant stress response, there is currently limited knowledge on the presence and functional and structural effects of phosphorylation on LEA proteins. In this study, we identified three phosphorylation sites (Ser(90), Tyr(136), and Thr(266)) in the soybean PM18 protein that belongs to the group-3 LEA proteins...
September 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28860774/bipolar-ii-disorder-as-the-initial-presentation-of-cadasil-an-underdiagnosed-manifestation
#20
Jianjun Wang, Jinfang Li, Fanxin Kong, Hanqing Lv, Zhouke Guo
Mood disturbances have been documented in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The highly varied morbidity indicates that the affective symptoms in CADASIL have not been cataloged systematically, leading to ineffective treatment, affecting the patients' quality of life, and possibly resulting in suicide. We present a case of CADASIL with bipolar II disorder as the first manifestation. A middle-aged female reported recurrent depressive episodes and appeared treatment resistant to adequate dosages and durations of antidepressants...
2017: Neuropsychiatric Disease and Treatment
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