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connexin 40

Sarah Falk
Pain is a major complication for cancer patients significantly compromising their quality of life. Current treatment is far from optimal and particularly bone-related cancer pain poses an increasing clinical and socio-economical problem. Connexins, key proteins in cell-cell communication, have the potential to affect cancer-induced bone pain at multiple levels, including nociceptive signaling and bone degradation. This study tested the analgesic potential of carbenoxolone, a broad-acting connexin blocker, in a mouse model of cancer-induced bone pain...
March 6, 2018: Pain
Yongqing Chen, Fangju Su, Juanping Han, Piqi Jiao, Wenyun Guo
To study the expression of Rho kinase (Rho associated coil forming protein kinase-1, ROCK-1) and its substrate myosin phosphatase target subunit 1 (myosin phosphatase target subunit-1, MYPT-1), connexin 40 (Cx40) and connexin 43 (Cx43) in the left atrial appendage of patients with atrial fibrillation, and explore the role of ROCK signaling pathway in patients with atrial fibrillation and its underlying mechanism. Methods: 40 patients undergoing open heart surgery were divided into two groups; atrial fibrillation group (AF group) and sinus rhythm group (SR group)...
February 19, 2018: Heart Surgery Forum
Jin Ma, Shiyu Ma, Chunxia Yin, Huanlin Wu
OBJECTIVE: The study aimed to investigate whether a Shengmai San-derived herbal, Fumai granule (FM), which had a preventive effect on atrial fibrillation (AF) in myocardial infarction (MI)-induced heart failure (HF) rat and to determine the underlying mechanisms. DESIGN AND METHODS: MI was induced by a ligation of the left anterior descending coronary artery. One week after MI surgery, FM was gavaged for 4 weeks. AF inducibility was detected by transesophageal programmed electrical stimulation technology...
February 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Dominik Steppan, Lisa Geis, Lin Pan, Kenneth Gross, Charlotte Wagner, Armin Kurtz
The so-called calcium paradoxon of renin describes the phenomenon that exocytosis of renin from juxtaglomerular cells of the kidney is stimulated by lowering of the extracellular calcium concentration. The yet poorly understood effect of extracellular calcium on renin secretion appears to depend on the function of the gap junction protein connexin 40 (Cx40) in renin-producing cells. This study aimed to elucidate the role of Cx40 for the calcium dependency of renin secretion in more detail by investigating if Cx40 function is really essential for the influence of extracellular calcium on renin secretion, if and how Cx40 affects intracellular calcium dynamics in renin-secreting cells and if Cx40-mediated gap junctional coupling of renin-secreting cells with the mesangial cell area is relevant for the influence of extracellular calcium on renin secretion...
February 9, 2018: Pflügers Archiv: European Journal of Physiology
Francesco Moccia
Intracellular Ca2+ signaling drives angiogenesis and vasculogenesis by stimulating proliferation, migration, and tube formation in both vascular endothelial cells and endothelial colony forming cells (ECFCs), which represent the only endothelial precursor truly belonging to the endothelial phenotype. In addition, local Ca2+ signals at the endoplasmic reticulum (ER)-mitochondria interface regulate endothelial cell fate by stimulating survival or apoptosis depending on the extent of the mitochondrial Ca2+ increase...
January 11, 2018: International Journal of Molecular Sciences
Nele Seemann, Andrea Welling, Ingo Rustenbeck
The antimalarial agent, mefloquine, inhibits the function of connexin Cx36 gap junctions and hemichannels and has thus become a tool to investigate their physiological relevance in pancreatic islets. In view of earlier reports on a KATP channel-block by mefloquine, the specificity of mefloquine as a pharmacological tool was investigated. Mouse pancreatic islets and single beta cells were used to measure membrane potential, whole cell currents, Ca2+ channel activity, cytosolic Ca2+ concentration ([Ca2+ ]i ) and insulin secretion...
December 5, 2017: Molecular and Cellular Endocrinology
Fei Zhang, Yuhao Bian, Lei Huang, Wenbin Fan
Structural and electrical remodeling within the atrium mediate the pathogenesis of atrial fibrillation (AF). Two key genes that sever a role in this remodeling are connexin 40 (Cx40) and potassium voltage-gated channel subfamily A member 5 (KCNA5), respectively. Electrical remodeling is considered to induce structural remodeling during AF. In the present study, the left atrial appendage section and atrial myocytes of patients with AF were evaluated. It was observed that Cx40 and KCNA5 mRNA (P<0.05) and protein (P<0...
November 2017: Experimental and Therapeutic Medicine
Ki-Ho Lee
Direct communication between neighboring cells through connexin (Cx)-based gap junction is a crucial biolo-gical manner to regulate functions of a tissue consisting of multi-cell types. The present research evaluated expressional changes of Cx isoforms in the caput epididymis of adult rat exposed to estradiol benzoate (EB) or flutamide (Flu) at the early postnatal age. A single subcutaneous administration of EB at a low-dose [0.015 µg /kg body weight (BW)] or a high-dose (1.5 µg/kg BW) or Flu at a low-dose (500 µg/kg BW) or a high-dose (5 mg/kg BW) was performed to an animal at 1 week of age...
September 2017: Balsaeng'gwa Saengsig
Rsituko Ohtani-Kaneko, Kenjiro Sato, Atsuhiro Tsutiya, Yuka Nakagawa, Kazutoshi Hashizume, Hidekatsu Tazawa
Induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) can contribute to elucidating the pathogenesis of heart and vascular diseases and developing their treatments. Their precise characteristics in fluid flow however remain unclear. Therefore, the aim of the present study is to characterise these features. We cultured three types of ECs in a microfluidic culture system: commercially available human iPS-ECs, human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs)...
October 9, 2017: Biomedical Microdevices
Jacques-Antoine Haefliger, Florent Allagnat, Lauriane Hamard, Loïc Le Gal, Paolo Meda, Denise Nardelli-Haefliger, Elisabeth Génot, Florian Alonso
OBJECTIVE: Cx40 (Connexin40) forms intercellular channels that coordinate the electric conduction in the heart and the vasomotor tone in large vessels. The protein was shown to regulate tumoral angiogenesis; however, whether Cx40 also contributes to physiological angiogenesis is still unknown. APPROACH AND RESULTS: Here, we show that Cx40 contributes to physiological angiogenesis. Genetic deletion of Cx40 leads to a reduction in vascular growth and capillary density in the neovascularization model of the mouse neonatal retina...
November 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Bo Zhang, Xun Cui, Hong-Hua Jin, Lan Hong, Xia Liu, Xiang Li, Qing-Gao Zhang, Li-Ping Liu
AIMS: Ginsenoside Re (G-Re), a major ginsenoside in ginseng, has many beneficial pharmacological effects on negative cardiac contractility, electromechanical alternans, antiarrhythmia, angiogenic regeneration and cardiac electrophysiological function. However, effects of G-Re on gap-junction remodeling are unclear. Therefore, this study aimed to investigate the effect of G-Re on angiotensin II (Ang II)-induced downregulation of connexin-40 (CX40) and -43 (CX43) in beating rat left atria...
December 1, 2017: Life Sciences
Eleftheria Pervolaraki, James Dachtler, Richard A Anderson, Arun V Holden
The developmental timeline of the human heart remains elusive. The heart takes on its characteristic four chambered appearance by ~56 days gestational age (DGA). However, owing to the complexities (both technical and logistical) of exploring development in utero, we understand little of how the ventricular walls develop. To address this, we employed diffusion tensor magnetic resonance imaging to explore the architecture and tissue organization of the developing heart aged 95-143 DGA. We show that fractional anisotropy increases (from ~0...
September 25, 2017: Scientific Reports
Jennifer J Hwa, Nathan Beckouche, Lawrence Huang, Yoseph Kram, Henrik Lindskog, Rong A Wang
The functions of blood flow in the morphogenesis of mammalian arteries and veins are not well understood. We examined the development of the dorsal aorta (DA) and the cardinal vein (CV) in Ncx1 (-/-) mutants, which lack blood flow due to a deficiency in a sodium calcium ion exchanger expressed specifically in the heart. The mutant DA and CV were abnormally connected. The endothelium of the Ncx1 (-/-) mutant DA lacked normal expression of the arterial markers ephrin-B2 and Connexin-40. Notch1 activation, known to promote arterial specification, was decreased in mutant DA endothelial cells (ECs), which ectopically expressed the venous marker Coup-TFII...
September 20, 2017: Scientific Reports
Taka-Aki Matsuyama, Hideo Tanaka, Hatsue Ishibashi-Ueda, Tetsuro Takamatsu
Surviving Purkinje fibers in myocardial infarct are regarded as an important substrate in arrhythmogenesis. However, poorly understood are functional properties of Purkinje fibers in the infarcted heart. We sought to visualize intracellular Ca(2+) ([Ca(2+)]i) dynamics of Purkinje fiber networks in the mouse myocardial infarct. Using 3- to 4-day-old or 7- to 9-day-old infarcted hearts after the left coronary-artery ligation corresponding, respectively, to acute or healing phase, we conducted rapid fluo4-fluorescence imaging on the endocardial surface of the left ventricular septum by macro-zoom fluorescence microscopy and rapid-scanning confocal microscopy...
November 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Benjamin Grimmer, Wolfgang Michael Kuebler
Hypoxic pulmonary vasoconstriction (HPV) in combination with hypercapnic pulmonary vasoconstriction redistributes pulmonary blood flow from poorly aerated to better ventilated lung regions by an active process of local vasoconstriction. Impairment of HPV results in ventilation-perfusion mismatch and is commonly associated with various lung diseases including pneumonia, sepsis, or cystic fibrosis. Although several regulatory pathways have been identified, considerable knowledge gaps persist, and a unifying concept of the signaling pathways that underlie HPV and their impairment in lung diseases has not yet emerged...
August 31, 2017: Journal of Applied Physiology
Mehrdad Sheikhvatan, Mohammadali Boroumand, Mehrdad Behmanesh, Seyed Hesameddin Abbasi, Gholamreza Davoodi, Shayan Ziaee, Sara Cheraghi
Background: The C1019T polymorphism of the connexin-37 (GJA4) gene is a single-nucleotide polymorphisms involved in atherosclerotic plaque rupture and atherosclerosis predisposition. We examined the association between the C1019T polymorphism of the GJA4 gene and the occurrence of myocardial infarction (MI) in patients with premature coronary artery disease (CAD). Methods: Our study recruited 1000 patients with the final diagnosis of premature CAD and classified them into 2 groups: with a history of MI (n = 461) and without it (n = 539)...
April 2017: Journal of Tehran Heart Center
Karin Macfelda, Barbara Kapeller, Alexander Holly, Bruno K Podesser, Udo Losert, Kersten Brandes, Peter Goettel, Johannes Mueller
AIMS: Beyond the influence of stimulating devices on cardiac excitation, their use in treating patients with heart failure has positive effects on the myocardium at the molecular level. Electrical signals can induce a wide spectrum of effects in living tissue. Therefore, we sought to determine whether applying electrical microcurrent directly to failing hearts leads to functional improvement. METHODS AND RESULTS: Sixteen male spontaneously hypertensive rats (SHRs) with heart failure underwent application of a patch electrode to the left ventricular epicardium and placement of a subcutaneous counter electrode...
August 2017: ESC Heart Failure
Yun Qiao, Catherine Lipovsky, Stephanie Hicks, Somya Bhatnagar, Gang Li, Aditi Khandekar, Robert Guzy, Kel Vin Woo, Colin G Nichols, Igor R Efimov, Stacey Rentschler
RATIONALE: Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes. OBJECTIVE: To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility. METHODS AND RESULTS: To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD])...
August 18, 2017: Circulation Research
Karel Tyml
Sepsis, life-threatening organ dysfunction caused by a dysfunctional host response to infection, is associated with high mortality. A promising strategy to improve the outcome is to inject patients intravenously with ascorbate (vitamin C). In animal models of sepsis, this injection improves survival and, among others, the microvascular function. This review examines our recent work addressing ascorbate's ability to inhibit arteriolar dysfunction and capillary plugging in sepsis. Arteriolar dysfunction includes impaired vasoconstriction/dilation (previously reviewed) and impaired conduction of vasoconstriction/dilation along the arteriole...
June 29, 2017: Antioxidants (Basel, Switzerland)
Frederic Pouille, Thomas S McTavish, Lawrence E Hunter, Diego Restrepo, Nathan E Schoppa
KEY POINTS: Despite sparse connectivity, population-level interactions between mitral cells (MCs) and granule cells (GCs) can generate synchronized oscillations in the rodent olfactory bulb. Intraglomerular gap junctions between MCs at the same glomerulus can greatly enhance synchronized activity of MCs at different glomeruli. The facilitating effect of intraglomerular gap junctions on interglomerular synchrony is through triggering of mutually synchronizing interactions between MCs and GCs...
September 1, 2017: Journal of Physiology
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