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Late sodium current

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https://www.readbyqxmd.com/read/28972668/wenxin-keli-diminishes-ca-2-overload-induced-by-hypoxia-reoxygenation-in-cardiomyocytes-through-inhibiting-inal-and-ical
#1
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 Ca(2+) ([Ca(2+) ]i ) overload via the stimulated reverse Na(+) -Ca(2+) 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 Ca(2+) current (ICaL ) and action potentials (APs) were recorded using the whole-cell patch-clamp technique in rabbit ventricular myocytes...
October 3, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28971840/selective-inhibition-of-physiological-late-sodium-current-stabilizes-ventricular-repolarization
#2
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
#3
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
#4
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
#5
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-mpfc-pyramidal-neurons-in-rats
#6
Maciej Gawlak, Bartłomiej Szulczyk, Adam Berlowski, Katarzyna Grzelka, Anna Stachurska, Justyna Pelka, Katarzyna Czarzasta, Maciej Malecki, Przemyslaw Kurowski, Ewa Nurowska, Pawel 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 (6-7-month-old) rats...
September 15, 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
#7
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
#8
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
https://www.readbyqxmd.com/read/28842436/ca-2-calmodulin-kinase-ii-dependent-regulation-of-atrial-myocyte-late-na-current-ca-2-cycling-and-excitability-a-mathematical-modeling-study
#9
Birce Onal, Daniel Gratz, Thomas J Hund
Atrial fibrillation (AF) affects more than 3 million people per year in the U.S., and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in regulation of persistent "late" sodium current (INa,L) has been identified. While INa,L inhibition is emerging as a potential antiarrhythmic strategy in AF patients, little is known about the mechanism linking INa,L to atrial arrhythmogenesis...
August 25, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28837385/mechanisms-and-models-of-cardiac-sodium-channel-inactivation
#10
Kathryn E Mangold, Brittany D Brumback, Paweorn Angsutararux, Taylor L Voelker, Wandi Zhu, Po Wei Kang, Jonathan D Moreno, Jonathan R Silva
Shortly after cardiac Na(+) channels activate and initiate the action potential, inactivation ensues within milliseconds, attenuating the peak Na(+) current, INa, and allowing the cell membrane to repolarize. A very limited number of Na(+) channels that do not inactivate carry a persistent INa, or late INa. While late INa is only a small fraction of peak magnitude, it significantly prolongs ventricular action potential duration, which predisposes patients to arrhythmia. Here, we review our current understanding of inactivation mechanisms, their regulation, and how they have been modeled computationally...
August 24, 2017: Channels
https://www.readbyqxmd.com/read/28756335/computational-approaches-to-understand-the-adverse-drug-effect-on-potassium-sodium-and-calcium-channels-for-predicting-tdp-cardiac-arrhythmias
#11
Mohsen Sharifi
Ion channels play a crucial role in the cardiovascular system. Our understanding of cardiac ion channel function has improved since their first discoveries. The flow of potassium, sodium and calcium ions across cardiomyocytes is vital for regular cardiac rhythm. Blockage of these channels, delays cardiac repolarization or tend to shorten repolarization and may induce arrhythmia. Detection of drug risk by channel blockade is considered essential for drug regulators. Advanced computational models can be used as an early screen for torsadogenic potential in drug candidates...
July 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28756098/phenotypic-variability-in-lqt3-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-and-their-response-to-antiarrhythmic-pharmacologic-therapy-an-in-silico-approach
#12
Michelangelo Paci, Elisa Passini, Stefano Severi, Jari Hyttinen, Blanca Rodriguez
BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are in vitro models with the clear advantages of their human origin and suitability for human disease investigations. However, limitations include their incomplete characterization and variability reported in different cell lines and laboratories. OBJECTIVE: The purpose of this study was to investigate in silico ionic mechanisms potentially explaining the phenotypic variability of hiPSC-CMs in long QT syndrome type 3 (LQT3) and their response to antiarrhythmic drugs...
July 27, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28734073/differential-calcium-sensitivity-in-nav-1-5-mixed-syndrome-mutants
#13
Mena Abdelsayed, Alban-Elouen Baruteau, Karen Gibbs, Shubhayan Sanatani, Andrew D Krahn, Vincent Probst, Peter C Ruben
KEY POINTS: SCN5a mutations may express gain-of-function (Long QT Syndrome-3), loss-of-function (Brugada Syndrome 1) or both (mixed syndromes), depending on the mutation and environmental triggers. One such trigger may be an increase in cytosolic calcium, accompanying exercise. Many mixed syndromes mutants, including ∆KPQ, E1784K, 1795insD and Q1909R, are found in calcium-sensitive regions. Elevated cytosolic calcium attenuates gain-of-function properties in ∆KPQ, 1795insD and Q1909R, but not in E1784K...
September 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28701305/redox-and-activation-of-protein-kinase-a-dysregulates-calcium-homeostasis-in-pulmonary-vein-cardiomyocytes-of-chronic-kidney-disease
#14
Shih-Yu Huang, Yao-Chang Chen, Yu-Hsun Kao, Ming-Hsiung Hsieh, Yung-Kuo Lin, Shih-Ann Chen, Yi-Jen Chen
BACKGROUND: Chronic kidney disease (CKD) increases the occurrence of atrial fibrillation and pulmonary vein (PV) arrhythmogenesis. Calcium dysregulation and reactive oxygen species (ROS) enhance PV arrhythmogenic activity. The purposes of this study were to investigate whether CKD modulates PV electrical activity through dysregulation of calcium homeostasis and ROS. METHODS AND RESULTS: Biochemical and electrocardiographic studies were conducted in rabbits with and without CKD (induced by 150 mg/kg per day neomycin sulfate and 500 mg/kg per day cefazolin)...
July 12, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28692548/comparison-of-vernakalant-and-ranolazine-in-atrial-fibrillation
#15
Gerrit Frommeyer, Magdalena Sterneberg, Dirk G Dechering, Simon Kochhäuser, Nils Bögeholz, Michael Fehr, Lars Eckardt
BACKGROUND: Current guidelines recommend vernakalant for pharmacologic cardioversion of recent-onset atrial fibrillation. However, this drug is not established as chronic therapy. METHODS AND RESULTS: In total, 15 rabbit hearts were Langendorff-perfused. A burst pacing protocol-induced atrial fibrillation in 7 of 15 hearts at baseline (10 episodes). Subsequently, a combination of acetylcholine and isoproterenol (ACH/ISO) has been administered to increase occurrence of atrial fibrillation resulting in a reduction of atrial action potential duration (-25 ms, P < 0...
September 2017: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/28654510/late-ina-inhibition-as-an-antiarrhythmic-strategy
#16
Alexander Burashnikov
Late sodium channel current (late INa) is considered to be an anti-arrhythmic target. The prime anti-arrhythmic mechanisms of late INa inhibition have been suggested to be 1) suppression of intracellular calcium [Cai]-mediated rhythmic activity (via reduction of Cai secondary to the decrease of intracellular sodium [Nai]) and 2) normalization of repolarization. Endogenous late INa is a small current and acceleration of heart rate decreases late INa density. Late INa influx may significantly contribute to Nai loading, but it appears to largely occur in the combined conditions of augmented late INa density, bradycardia, and prolonged repolarization...
June 22, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28554967/basal-late-sodium-current-is-a-significant-contributor-to-the-duration-of-action-potential-of-guinea-pig-ventricular-myocytes
#17
Yejia Song, Luiz Belardinelli
In cardiac myocytes, an enhancement of late sodium current (INaL) under pathological conditions is known to cause prolongation of action potential duration (APD). This study investigated the contribution of INaL under basal, physiological conditions to the APD Whole-cell INaL and the APD of ventricular myocytes isolated from healthy adult guinea pigs were measured at 36°C. The INaL inhibitor GS967 or TTX was applied to block INaL The amplitude of basal INaL and the APD at 50% repolarization in myocytes stimulated at a frequency of 0...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28552050/readthrough-of-scn5a-nonsense-mutations-r1623x-and-s1812x-question-gene-therapy-in-brugada-syndrome
#18
Siyong Teng, Jian Huang, Zhan Gao, Jie Hao, Yuejin Yang, Shu Zhang, Jielin Pu, Rutai Hui, Yongjian Wu, Zheng Fan
PURPOSE: Readthrough of nonsense mutation are used as gene-specific treatment in some genetic disease. Response to readthrough treatment is determined by readthrough efficiency of various nonsense mutations. In this manuscript, we aimed to explore the harmful effect of nonsense mutation suppressions. METHODS: HEK293 cells were transfected with two SCN5A (encode cardiac Na+ channel) nonsense mutations, p.R1623X and p.S1812X. We applied two readthrough-enhancing methods (either aminoglycosides or by a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1)) to suppress these SCN5A nonsense mutations...
May 28, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28530796/what-do-laser-induced-transient-techniques-reveal-for-batteries-na-and-k-intercalation-from-aqueous-electrolytes-as-an-example
#19
Daniel Scieszka, Jeongsik Yun, Aliaksandr S Bandarenka
Technological advancement has been revolutionized by rechargeable batteries, without which the use of various modern devices would not be possible. Aqueous Na ion batteries have lately garnered much attention, being recognized as a promising alternative to the commonly used Li ion batteries for the large-scale energy storage systems. However, further improvement and optimization of such systems require a more detailed understanding of intercalation mechanisms. In this work, we for the first time demonstrate the implementation of the laser-induced current transient (LICT) technique for in situ characterization of battery systems and investigate the interface between Na2Ni[Fe(CN)6] model battery electrodes and aqueous electrolytes in contact with aqueous electrolytes...
May 31, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28527083/shared-mechanisms-of-epilepsy-migraine-and-affective-disorders
#20
Davide Zarcone, Simona Corbetta
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility...
May 2017: Neurological Sciences
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