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gap junctions

Lingfeng Meng, Albert Zhang, Yishi Jin, Dong Yan
Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4...
October 21, 2016: ELife
Kishan A Manani, Kim Christensen, Nicholas S Peters
Atrial fibrillation (AF) increases the risk of stroke by a factor of 4-5 and is the most common abnormal heart rhythm. The progression of AF with age, from short self-terminating episodes to persistence, varies between individuals and is poorly understood. An inability to understand and predict variation in AF progression has resulted in less patient-specific therapy. Likewise, it has been a challenge to relate the microstructural features of heart muscle tissue (myocardial architecture) with the emergent temporal clinical patterns of AF...
October 2016: Physical Review. E
Lois Choy, Jie Ming Yeo, Vivian Tse, Shing Po Chan, Gary Tse
The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony...
September 2016: IJC Heart & Vasculature
Chien-Cheng Chen, Chan-Yen Kuo, Rong-Fu Chen
Background: Cardiomyocyte under hypoxia cause cell death or damage is associated with heart failure. Gap junction, such as connexin 43 play a role in regulation of heart function under hypoxia. Caffeic acid phenethyl ester (CAPE) has been reported as an active component of propolis, has antioxidative, anti-inflammatory antiproliferative and antineoplastic biological properties. Aims: Connexin 43 appear to have a critical role in heart failure under hypoxia, there has been considerable interest in identifying the candidate component or compound to reduce cell death...
2016: International Journal of Medical Sciences
Juan Rodriguez-Paris, Jörg Waldhaus, Jeenal A Gordhandas, Lynn Pique, Iris Schrijver
We characterized a novel GJB2 missense variant, c.133G>A, p.Gly45Arg, and compared it with the only other variant at the same amino acid position of the connexin 26 protein (Cx26) reported to date: c.134G>A, p.Gly45Glu. Whereas both variants are associated with hearing loss and are dominantly inherited, p.Gly45Glu has been implicated in the rare fatal keratitis-ichthyosis-deafness (KID) syndrome, which results in cutaneous infections and septicemia with premature demise in the first year of life. In contrast, p...
2016: PeerJ
Chris Amdisen, Anna K Keller, Rie Schultz Hansen, Rikke Nørregaard, Søren Palmelund Krag, Ulla Møldrup, Michael Pedersen, Bente Jespersen, Henrik Birn
INTRODUCTION: Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up...
2016: PloS One
A J Korzekwa, M Łupicka, B M Socha, A A Szczepańska
Adenomyosis is defined as the presence of glandular foci external to the endometrium of the uterus, either in the myometrium or/and perimetrium, depending on the progress of this dysfunction. To date, we showed that steroids secretion and prolactin expression and proliferative processes are disturbed during uterine adenomyosis in cows. During endometriosis in eutopic endometrium in women, gap junctions are down regulated. The transmembrane gap junction protein, connexin (Cx43) is necessary for endometrial morphological, biochemical and angiogenic functions...
September 1, 2016: Polish Journal of Veterinary Sciences
Rita I Jabr, Fiona S Hatch, Samantha C Salvage, Alejandro Orlowski, Paul D Lampe, Christopher H Fry
Cardiac arrhythmias are associated with raised intracellular [Ca(2+)] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca(2+)-dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
Pasquale Striano, Vincenzo Belcastro, Antonietta Coppola, Carlo Minetti, Salvatore Striano
INTRODUCTION: Despite optimal medical treatment, up to 30% of patients with epilepsy continue to experience recurrent seizures, and the challenge for new more efficacious and better-tolerated drugs is continuing. New antiepileptic drugs include the evolution of preexisting drugs and new compounds identified through the investigation of additional molecular targets, such as SV2A synaptic vesicle protein, voltage-gated potassium channels, ionotropic and metabotropic glutamate receptors, and gap junctions...
October 5, 2016: Clinical Neuropharmacology
Jian-Feng Wu, Jie Ji, Shu-Ying Dong, Bei-Bei Li, Mei-Ling Yu, Dan-Dan Wu, Liang Tao, Xu-Hui Tong
Chemotherapeutic drug-induced apoptosis is enhanced by gap junction intercellular communication (GJIC) in a variety of tumor cells. Oxaliplatin and gefitinib are the most widely used chemotherapeutic drugs. However, the synergistic influence remains unknown in testicular cancer chemotherapy. The aim of the present study was to investigate the apoptosis induced by oxaliplatin combined with gefitinib and the potential mechanisms in I-10 testicular cancer cells. The results showed that gefitinib significantly enhanced oxaliplatin-induced apoptosis...
October 11, 2016: Oncology Reports
Zhao-Wei Zou, Hai-Jin Chen, Jin-Long Yu, Zong-Hai Huang, Shun Fang, Xiao-Hua Lin
Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5‑fluorouracil (5‑FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock‑down...
October 6, 2016: Molecular Medicine Reports
Li-Jie Wang, Wei-Dong Liu, Liang Zhang, Ke-Tao Ma, Lei Zhao, Wen-Yan Shi, Wen-Wen Zhang, Ying-Zi Wang, Li Li, Jun-Qiang Si
Niflumic acid (NFA) is a novel gap junction (GJ) inhibitor. The aim of the present study was to investigate the effect of NFA on GJ communication and the expression of connexin (Cx) in vascular smooth muscle cells (VSMCs) of mesenteric arterioles of spontaneously hypertensive rats (SHR). Whole‑cell patch clamp recording demonstrated that NFA at 1x10‑4 M significantly inhibited the inward current and its effect was reversible. The time for charging and discharging of cell membrane capacitance (Cinput) reduced from 9...
September 26, 2016: Molecular Medicine Reports
H Mike Kim, Colin R Andrews, Evan P Roush, Gregory I Pace, Gregory S Lewis
BACKGROUND: Double-strand lateral ulnar collateral ligament (LUCL) reconstruction is an effective treatment for posterolateral rotatory instability (PLRI) of the elbow, but anatomic landmarks for ulnar tunnel placement are often difficult to identify intraoperatively, which potentially can result in a nonanatomic LUCL reconstruction. This study investigated the effect of ulnar tunnel location on joint stability in double-strand LUCL reconstruction. METHODS: PLRI was artificially created in 7 cadaveric elbows, and double-strand LUCL reconstruction was performed...
October 10, 2016: Journal of Shoulder and Elbow Surgery
Prateek Mahalwar, Ajeet Pratap Singh, Andrey Fadeev, Christiane Nüsslein-Volhard, Uwe Irion
The conspicuous striped coloration of zebrafish is produced by cell-cell interactions among three different types of chromatophores: black melanophores, orange/yellow xanthophores and silvery/blue iridophores. During color pattern formation xanthophores undergo dramatic cell shape transitions and acquire different densities, leading to compact and orange xanthophores at high density in the light stripes, and stellate, faintly pigmented xanthophores at low density in the dark stripes. Here, we investigate the mechanistic basis of these cell behaviors in vivo, and show that local, heterotypic interactions with dense iridophores regulate xanthophore cell shape transition and density...
October 14, 2016: Biology Open
Taizen Nakase, Tatsuya Ishikawa, Hajime Miyata
Fragility of atheromatous plaque in the internal carotid artery can be a risk of brain infarction. The activation of macrophages by oxidative stress and the vulnerability of vascular endothelial cells have been reported to participate in the fragility of atheromatous plaque. Therefore, from the view point of prevention of brain infarction, we investigated the pathological factors which may influence the stabilization of atheromatous plaque. Patients undertaking carotid endoarterectomy (CEA) were continuously screened...
October 13, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Hongmei Liu, Hisashi Kondo, Takahisa Ohno
Utilizing first-principles theory, we demonstrate that half-metallicity can be realized in a junction composed of non-magnetic armchair graphene nanoribbon (AGNR) and ferromagnetic Ni electrodes. The half-metallic property originates from the AGNR energy gap of the up spin located at the Fermi energy, while large electronic states are generated for the down spin. By altering the interlayer distance and the contact area, namely, the strength of AGNR-Ni interaction, the efficiency of the spin filter becomes lower, since the energy gap moves away from the Fermi energy with the variation of charge transfer intensity...
December 2016: Nanoscale Research Letters
Daniel Torralba, Francesc Baixauli, Francisco Sánchez-Madrid
Mitochondria regulate multiple cell processes, including calcium signaling, apoptosis and cell metabolism. Mitochondria contain their own circular genome encoding selected subunits of the oxidative phosphorylation complexes. Recent findings reveal that, in addition to being maternally inherited, mitochondria can traverse cell boundaries and thus be horizontally transferred between cells. Although, the physiological relevance of this phenomenon is still under debate, mitochondria uptake rescues mitochondrial respiration defects in recipient cells and regulates signaling, proliferation or chemotherapy resistance in vitro and in vivo...
2016: Frontiers in Cell and Developmental Biology
Javier Cervera, Salvador Meseguer, Salvador Mafe
The single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions...
October 12, 2016: Scientific Reports
Onur Kilic, David Pamies, Emily Lavell, Paula Schiapparelli, Yun Feng, Thomas Hartung, Anna Bal-Price, Helena T Hogberg, Alfredo Quinones-Hinojosa, Hugo Guerrero-Cazares, Andre Levchenko
Migration of neural progenitors in the complex tissue environment of the central nervous system is not well understood. Progress in this area has the potential to drive breakthroughs in neuroregenerative therapies, brain cancer treatments, and neurodevelopmental studies. To a large extent, advances have been limited due to a lack of controlled environments recapitulating characteristics of the central nervous system milieu. Reductionist cell culture models are frequently too simplistic, and physiologically more relevant approaches such as ex vivo brain slices or in situ experiments provide little control and make information extraction difficult...
October 18, 2016: Lab on a Chip
Nicholas A Early, John J Elias, Steven B Lippitt, Danielle E Filipkowski, Robert A Pedowitz, William J Ciccone
BACKGROUND: This in vitro study evaluated the biomechanical benefit of adding spanning sutures to single-row rotator cuff repair. METHODS: Mechanical testing was performed to evaluate 9 pairs of cadaveric shoulders with complete rotator cuff repairs, with a single-row technique used on one side and the suture spanning technique on the other. The spanning technique included sutures from 2 lateral anchors securing tendon near the musculotendinous junction, spanning the same anchor placement from single-row repair...
October 5, 2016: Journal of Shoulder and Elbow Surgery
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