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Przemysław B Radwański, Hsiang-Ting Ho, Rengasayee Veeraraghavan, Lucia Brunello, Bin Liu, Andriy E Belevych, Sathya D Unudurthi, Michael A Makara, Silvia G Priori, Pompeo Volpe, Antonis A Armoundas, Wolfgang H Dillmann, Bjorn C Knollmann, Peter J Mohler, Thomas J Hund, Sándor Györke
BACKGROUND: Cardiac arrhythmias are a leading cause of death in the US. Vast majority of these arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with increased levels of circulating catecholamines and involve abnormal impulse formation secondary to aberrant Ca(2+) and Na(+) handling. However, the mechanistic link between β-AR stimulation and the subcellular/molecular arrhythmogenic trigger(s) remains elusive. METHODS AND RESULTS: We performed functional and structural studies to assess Ca(2+) and Na(+) signaling in ventricular myocyte as well as surface electrocardiograms in mouse models of cardiac calsequestrin (CASQ2)-associated CPVT...
June 2016: JACC. Basic to Translational Science
Sophie Le Page, Marjorie Niro, Jérémy Fauconnier, Laura Cellier, Sophie Tamareille, Abdallah Gharib, Arnaud Chevrollier, Laurent Loufrani, Céline Grenier, Rima Kamel, Emmanuelle Sarzi, Alain Lacampagne, Michel Ovize, Daniel Henrion, Pascal Reynier, Guy Lenaers, Delphine Mirebeau-Prunier, Fabrice Prunier
BACKGROUND: Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain. OBJECTIVES: To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries. METHODS AND RESULTS: We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates...
2016: PloS One
Alessandra Forni, Stefano Pieraccini, Davide Franchini, Maurizio Sironi
Halogen bonding, a noncovalent interaction between a halogen atom and a nucleophilic site, is receiving a growing attention in the chemical community stimulating a large number of theoretical investigations. The DFT approach revealed to be one of the most suitable methods owing to its accuracy and low computational cost. We report here a detailed analysis of the performance of an extensive set of DFT functionals in reproducing accurate binding energies and topological properties for the halogen bonding interaction of either NCX or PhX molecules (X = F, Cl, Br, I) with the aromatic system of benzene in the T-shaped configuration...
October 10, 2016: Journal of Physical Chemistry. A
Felix Hohendanner, Jaime DeSantiago, Frank R Heinzel, Lothar A Blatter
We tested the hypothesis that in atrial myocytes from a rabbit left ventricular heart failure (HF) model, spatial inhomogeneity and temporal dyssynchrony of Ca removal during excitation-contraction coupling together with increased Na/Ca exchange (NCX) activity generates a substrate for proarrhythmic Ca release. Ca removal occurs via Ca reuptake into the sarcoplasmic reticulum and extrusion via NCX exclusively in the cell periphery since rabbit atrial myocytes lack transverse tubules. Ca removal kinetics were assessed by the time constant τ of decay of local peripheral subsarcolemmal (SS) and central (CT) action potential (AP) induced Ca transients (CaTs) recorded in confocal line scan mode (using Fluo-4)...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Kengo Fukuoka, Satoshi Nara, Yoshitaka Honma, Yoji Kishi, Minoru Esaki, Kazuaki Shimada
BACKGROUND: Recently, an increasing number of patients with liver metastases from colorectal cancer have received chemotherapy before hepatectomy. However, the effect of chemotherapy on postoperative short-term outcome is not well defined. METHODS: We retrospectively investigated the postoperative complications of 439 patients who underwent hepatectomy for colorectal liver metastases in our division from 2005 to 2014. Patients were classified into two groups according to the presence (Cx; 84 patients) or absence (NCx; 355 patients) of preoperative chemotherapy...
September 27, 2016: World Journal of Surgery
Miyuki Tashiro, Yasuhide Watanabe, Tomomi Yamakawa, Kanna Yamashita, Satomi Kita, Takahiro Iwamoto, Junko Kimura
BACKGROUND AND AIMS: Carvedilol ((+/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), a β-adrenoceptor-blocker, has multi-channel blocking and vasodilator properties. This agent dose-dependently improves left ventricular function and reduces mortality in patients with arrhythmia and chronic heart failure. However, the effect of carvedilol on the cardiac Na+/Ca2+ exchanger (NCX1) has not been investigated. METHODS AND RESULTS: We examined the effects of carvedilol and metoprolol, 2 β-blockers, on Na+/Ca2+ exchange current (INCX) in guinea-pig cardiac ventricular cells and fibroblasts expressing dog cardiac NCX1...
September 28, 2016: Pharmacology
Nihal Ozturk, Yusuf Olgar, Hakan Er, Murathan Kucuk, Semir Ozdemir
BACKGROUND: The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. METHODS: For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C...
September 26, 2016: Cardiology Journal
Qiongying Wang, An Xie, Han Xu, Jing Yu
OBJECTIVE: Abnormal Ca handling is thought to be related with triggered activity and mitochondria participate in Ca homeostasis. We evaluated the contribution of Astragaloside IV (ASI) for mitochondrial ROS and Ca Flux to cardiac function by using DOCA-salt hypertensive mice. DESIGN AND METHOD: We used the deoxycorticosterone acetate (DOCA)-salt mouse model. The ventricular myocytes isolated from mice was utilized for action potentials (APs) recording, potassium and L-type Ca currents...
September 2016: Journal of Hypertension
A P Rosa, C E V Bonilla, A Londero, C B S Giacomini, C Orso, M O Fernandes, J S Moura, R Hermes
The aim of study was to evaluate the effect on broiler breeders fed with corn or sorghum diets and canthaxanthin on lipid peroxidation, fatty acid, and offspring's performance. A total of 440 females with similar body weight (BW) (3.77 ± 0.11 kg) and 60 roosters were placed in an open-sided house with 20 pens, randomly distributed in a factorial arrangement (2 × 2). There were 4 diets of 2 ingredients; corn (CO) or sorghum (SO) and 2 levels of canthaxanthin; 6 mg/kg (CX) and 0 mg/kg (NCX) totaling five replicate pens of 22 females and 3 males each, from 45 to 65 wk old...
September 6, 2016: Poultry Science
Xiaofei Yan, Meng Xun, Jing Li, Litao Wu, Xiaojuan Dou, Jin Zheng
Hyperglycemia is one of the major factors responsible for the myocardial apoptosis and dysfunction in diabetes. Many studies have proved that there is a close relationship between decreased Na(+)/K(+)-ATPase activity and diabetic cardiomyopathy. However, the effect of directly activated Na(+)/K(+)-ATPase on high glucose-induced myocardial injury is still unknown. Here we found that DRm217, a Na(+)/K(+)-ATPase's DR-region specific monoclonal antibody and direct activator, could prevent high glucose-induced H9c2 cell injury, reactive oxygen species (ROS) release, and mitochondrial dysfunction...
October 2016: Acta Biochimica et Biophysica Sinica
Ricardo De Pascual, Inés Colmena, Lucía Ruiz-Pascual, Andrés Mateo Baraibar, Javier Egea, Luis Gandía, Antonio G García
It is known that the sustained depolarisation of adrenal medullary bovine chromaffin cells (BCCs) with high K(+) concentrations produces an initial sharp catecholamine release that subsequently fades off in spite depolarisation persists. Here, we have recreated a sustained depolarisation condition of BCCs by treating them with the Na(+)/K(+) ATPase blocker ouabain; in doing so, we searched experimental conditions that permitted the development of a sustained long-term catecholamine release response that could be relevant during prolonged stress...
October 2016: Pflügers Archiv: European Journal of Physiology
Amir Geramipour, Zsófia Kohajda, Claudia Corici, János Prorok, Zsolt Szakonyi, Kinga Oravecz, Zoltán Márton, Norbert Nagy, András Tóth, Károly Acsai, László Virág, András Varró, Norbert Jost
The sodium-calcium exchanger (NCX) is considered as the major transmembrane transport mechanism that controls Ca(2+) homeostasis. Its contribution to the cardiac repolarization has not yet been directly studied due to lack of specific inhibitors, so that an urgent need for more selective compounds. In this study, the electrophysiological effects of GYKB-6635, a novel NCX inhibitor, on the NCX, L-type calcium, and main repolarizing potassium currents as well as action potential (AP) parameters were investigated...
July 1, 2016: Canadian Journal of Physiology and Pharmacology
Bijay Limbu, Kushal Shah, Seth H Weinberg, Makarand Deo
Cardiac Purkinje cells (PCs) are morphologically and electrophysiologically different from ventricular myocytes and, importantly, exhibit distinct calcium (Ca(2+)) homeostasis. Recent studies suggest that PCs are more susceptible to action potential (AP) abnormalities than ventricular myocytes; however, the exact mechanisms are poorly understood. In this study, we utilized a detailed biophysical mathematical model of a murine PC to systematically examine the role of cytosolic Ca(2+) diffusion in shaping the AP in PCs...
2016: Clinical Medicine Insights. Cardiology
Maike Friess, Jens Hammann, Petr Unichenko, Heiko J Luhmann, Robin White, Sergei Kirischuk
Myelination in the central nervous system depends on axon-oligodendrocyte precursor cell (OPC) interaction. We suggest that myelin synthesis may be influenced by [Na(+)]i and [Ca(2+)]i signaling in OPCs. Experiments were performed in mouse cultured OPCs at day in vitro (DIV) 2-6 or acute slices of the corpus callosum at postnatal days (P) 10-30. Synthesis of Myelin Basic Protein (MBP), an "executive molecule of myelin", was used as readout of myelination. Immunohistological data revealed that MBP synthesis in cultured OPCs starts around DIV4...
June 29, 2016: Cell Calcium
Kazuhiro Nishiyama, Yasu-Taka Azuma, Ai Morioka, Natsuho Yoshida, Midori Teramoto, Kohta Tanioka, Satomi Kita, Satomi Hayashi, Hidemitsu Nakajima, Takahiro Iwamoto, Tadayoshi Takeuchi
The Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1...
October 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Bei Liu, Lixia Yang, Bin Zhang, Chenwei Kuang, Shiliang Huang, Ruiwei Guo
BACKGROUND: The reverse mode of Na(+)/Ca(2+) exchanger (NCX) 1 can transport Ca(2+) into cells and is involved in the contractile regulation of vascular smooth muscle cells (VSMCs) and the development of hypertension. We hypothesized that upregulation of NCX1 expression induced by angiotensin II (Ang II) could be dependent on activation of nuclear factor-kappa B (NF-κB) and contributes to Ca(2+) influx in VSMCs. METHODS: An osmotic minipump was implanted for administration of Ang II in Sprague-Dawley rats, and blood pressure, as well as NCX1 expression, in the aorta was measured...
February 27, 2016: Canadian Journal of Cardiology
Torsten Christ, Peter P Kovács, Karoly Acsai, Michael Knaut, Thomas Eschenhagen, Norbert Jost, András Varró, Erich Wettwer, Ursula Ravens
The Na(+)/Ca(2+) exchanger (NCX) plays a major role in myocardial Ca(2+) homoeostasis, but is also considered to contribute to the electrical instability and contractile dysfunction in chronic atrial fibrillation (AF). Here we have investigated the effects of the selective NCX blocker SEA0400 in human right atrial cardiomyocytes from patients in sinus rhythm (SR) and AF in order to obtain electrophysiological evidence for putative antiarrhythmic activity of this new class of drugs. Action potentials were measured in right atrial trabeculae using conventional microelectrodes...
October 5, 2016: European Journal of Pharmacology
Mariana Argenziano, Gisela Tiscornia, Rosalia Moretta, Leonardo Casal, Constanza Potilinski, Carlos Amorena, Eduardo Garcia Gras
In most species androgens shorten the cardiac action potential and reduce the risk of afterdepolarizations. Despite the central role of the rat model in physiological studies, the effects of androgens on the rat heart are still inconclusive. We therefore performed electrophysiological studies on the perfused rat right ventricular free wall. We found a correlation between androgenic activity and a propensity to generate ventricular ectopic action potentials. We also found that the testosterone treatment increased action potential duration at 90 % of repolarization (APD90), while androgenic inhibition increased the time to peak and decreased APD90...
May 30, 2016: Journal of Physiological Sciences: JPS
Maria Barthmes, Jun Liao, Youxing Jiang, Andrea Brüggemann, Christian Wahl-Schott
Sodium-calcium exchangers (NCXs) are membrane transporters that play an important role in Ca(2+) homeostasis and Ca(2+) signaling. The recent crystal structure of NCX_Mj, a member of the NCX family from the archaebacterium Methanococcus jannaschii, provided insight into the atomistic details of sodium-calcium exchange. Here, we extend these findings by providing detailed functional data on purified NCX_Mj using solid supported membrane (SSM)-based electrophysiology, a powerful but unexploited tool for functional studies of electrogenic transporter proteins...
June 2016: Journal of General Physiology
Yuki Kurauchi, Akinori Hisatsune, Takahiro Seki, Hiroshi Katsuki
Cerebrovascular endothelial cell dysfunction resulting in imbalance of cerebral blood flow contributes to the onset of psychiatric disorders such as depression, schizophrenia and bipolar disorder. Although decrease in Na(+), K(+)-ATPase activity has been reported in the patients with schizophrenia and bipolar disorder, the contribution of Na(+), K(+)-ATPase to endothelial cell dysfunction remains poorly understood. Here, by using rat neonatal prefrontal cortex slice cultures, we demonstrated that pharmacological inhibition of Na(+), K(+)-ATPase by ouabain induced endothelial cell injury...
August 1, 2016: Brain Research
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