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https://www.readbyqxmd.com/read/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#1
Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff, Albrecht Schwab
Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all "hallmarks of cancer" such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899943/effects-of-allitridum-on-the-transient-outward-potassium-current-in-rats-with-heart-failure
#2
Xiao-Jing Zhao, Kun Lin, Yu Zhang, Bin Xu, Li Liu, Yi-Cheng Fu, Xi Chen, Zhong-Qi Cai, Zhi-Juan Wu, Yun Huang, Yang Li
OBJECTIVE: To study the effect of allitridum on the transient outward potassium current (Ito) of ventricular myocytes in heart failure (HF). METHODS: The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. RESULTS: The Ito current had a significant decrease in the HF group, compared with the control group...
September 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/27898427/cocaine-withdrawal-reduces-gamma-aminobutyric-acid-ergic-transmission-and-gephyrin-expression-at-medial-prefrontal-cortex-in-cocaine-conditioned-place-preference-rats-which-shows-increased-cocaine-seeking
#3
Wenqiong Yang, Hongsheng He, Yan Pan, Falan Duan, Dan Zhao, Bo Hu, Qingzhen Zhou, Wanhong Liu
AIMS: Chronic cocaine abuse decreases the inhibitory synaptic transmission via unknown mechanisms, while pharmacologically augmenting gamma-aminobutyric acid-ergic (GABAergic) transmission attenuates cocaine craving. Here, we propose that prolonged cocaine withdrawal downregulates GABAergic transmission and its important regulator gephyrin in medial prefrontal cortex (mPFC), in cocaine-conditioned place-preference (CPP) rats. METHODS: CPP test, patch clamp, and Western blot analysis are engaged to test this proposal...
November 30, 2016: European Addiction Research
https://www.readbyqxmd.com/read/27897242/cortical-synaptic-and-dendritic-spine-abnormalities-in-a-presymptomatic-tdp-43-model-of-amyotrophic-lateral-sclerosis
#4
Matthew J Fogarty, Paul M Klenowski, John D Lee, Joy R Drieberg-Thompson, Selena E Bartlett, Shyuan T Ngo, Massimo A Hilliard, Mark C Bellingham, Peter G Noakes
Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43(Q331K) mutation...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896651/postnatal-administration-of-dizocilpine-inhibits-neuronal-excitability-in-pfc-and-induces-social-deficits-detected-by-miceprofiler
#5
Dexiao Zhu, Hui Wang, Jintao Wu, Qian Wang, Ling Xu, Yue Zhao, Kunkun Pang, Qingqing Shi, Wenbo Zhao, Jing Zhang, Jinhao Sun
Schizophrenia is a devastating mental disease with social deficit as its core component of negative symptoms, which could be induced in rodents by dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist. NMDA receptors are highly expressed during the postnatal period. However, less attention has been paid to the effects of postnatal MK-801 administration on social interaction. In this study, we evaluated the effects of postnatal administration of MK-801 on social interaction and explored the possible mechanisms...
November 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27895555/spike-timing-rigidity-is-maintained-in-bursting-neurons-under-pentobarbital-induced-anesthetic-conditions
#6
Risako Kato, Masanori Yamanaka, Eiko Yokota, Noriaki Koshikawa, Masayuki Kobayashi
Pentobarbital potentiates γ-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission by prolonging the open time of GABAA receptors. However, it is unknown how pentobarbital regulates cortical neuronal activities via local circuits in vivo. To examine this question, we performed extracellular unit recording in rat insular cortex under awake and anesthetic conditions. Not a few studies apply time-rescaling theorem to detect the features of repetitive spike firing. Similar to these methods, we define an average spike interval locally in time using random matrix theory (RMT), which enables us to compare different activity states on a universal scale...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27889432/decrease-of-high-voltage-ca-2-currents-in-the-dentate-gyrus-granule-cells-by-entorhinal-amyloidopathy-is-reversed-by-calcium-channel-blockade
#7
Hamid Gholami Pourbadie, Nima Naderi, Hadi Mirzapour Delavar, Mahshid Hosseinzadeh, Nasrin Mehranfard, Fariba Khodagholi, Mahyar Janahmadi, Fereshteh Motamedi
In the Alzheimer's disease (AD), entorhinal-hippocampal circuit is one of the earliest affected networks. There are some evidences indicating abnormal neuronal excitability and impaired synaptic plasticity in the dentate gyrus (DG) of AD animal model. However, the underlying mechanism leading to DG dysfunction particularly in the early phase of AD is not known. Since calcium dyshomeostasis has a critical role in the etiology of AD, it is possible that this phenomenon precedes electrophysiological alteration in the DG...
November 24, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27888546/sex-differences-in-depolarizing-actions-of-gabaa-receptor-activation-in-rat-embryonic-hypothalamic-neurons
#8
Franco R Mir, Hugo F Carrer, María J Cambiasso
GABAA receptor activation exerts trophic actions in immature neurons through depolarization of resting membrane potential. The switch to its classical hyperpolarizing role is developmentally regulated. Previous results suggest that a hormonally biased sex difference exists at the onset of the switch in hypothalamic neurons. The aim of this work was to evaluate sex differences in GABAA receptor function of hypothalamic neurons before brain masculinization by gonadal hormones. Hypothalamic cells were obtained from embryonic day 16 male and female rat foetuses, 2 days before the peak of testosterone production by the foetal testis, and grown in vitro for 9 days...
November 5, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27888509/functional-properties-of-granule-cells-with-hilar-basal-dendrites-in-the-epileptic-dentate-gyrus
#9
Tony Kelly, Heinz Beck
OBJECTIVE: The maturation of adult-born granule cells and their functional integration into the network is thought to play a key role in the proper functioning of the dentate gyrus. In temporal lobe epilepsy, adult-born granule cells in the dentate gyrus develop abnormally and possess a hilar basal dendrite (HBD). Although morphological studies have shown that these HBDs have synapses, little is known about the functional properties of these HBDs or the intrinsic and network properties of the granule cells that possess these aberrant dendrites...
November 26, 2016: Epilepsia
https://www.readbyqxmd.com/read/27886375/modulation-of-chloride-currents-in-human-lung-epithelial-cells-exposed-to-exogenous-oxidative-stress
#10
Rita Canella, Marta Martini, Roberta Borriello, Carlotta Cavicchio, Ximena M Muresan, Mascia Benedusi, Franco Cervellati, Giuseppe Valacchi
Air pollution continues to be a major public health concern affecting 9 out of 10 individuals living in urban areas worldwide. Respiratory tract is the organ most exposed to gas pollution and ozone has been shown to be one of the most noxious pollutants to which living organisms are exposed. In the present work, we have investigated the effects of 0.1 ppm of ozone on chloride currents in human lung epithelial cells (A549 line) and whether this effect could be modulated by vitamin E pre-treatment. Whole-cell patch clamp technique was applied to not excitable cells in order to obtain information about chloride currents behavior, important for epithelial lung cells homeostasis...
November 25, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27884956/regional-effects-of-streptozotocin-induced-diabetes-on-shortening-and-calcium-transport-in-epicardial-and-endocardial-myocytes-from-rat-left-ventricle
#11
Manal M A Smail, Muhammad A Qureshi, Anatoliy Shmygol, Murat Oz, Jaipaul Singh, Vadym Sydorenko, Alya Arabi, Frank C Howarth, Lina Al Kury
In the heart, the left ventricle pumps blood at higher pressure than the right ventricle. Within the left ventricle, the electromechanical properties of ventricular cardiac myocytes vary transmurally and this may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. Diabetes is also associated with alterations in hemodynamic function. The aim of this study was to investigate shortening and Ca(2+) transport in epicardial (EPI) and endocardial (ENDO) left ventricular myocytes in the streptozotocin (STZ)-induced diabetic rat...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27881950/a-new-approach-of-modified-submerged-patch-clamp-recording-reveals-interneuronal-dynamics-during-epileptiform-oscillations
#12
Gareth Morris, Premysl Jiruska, John G R Jefferys, Andrew D Powell
Highlights Simultaneous epileptiform LFPs and single-cell activity can be recorded in the membrane chamber.Interneuron firing can be linked to epileptiform high frequency activity.Fast ripples, unique to chronic epilepsy, can be modeled in ex vivo tissue from TeNT-treated rats. Traditionally, visually-guided patch clamp in brain slices using submerged recording conditions has been required to characterize the activity of individual neurons. However, due to limited oxygen availability, submerged conditions truncate fast network oscillations including epileptiform activity...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27881847/epigenetic-regulation-of-l-type-voltage-gated-ca-2-channels-in-mesenteric-arteries-of-aging-hypertensive-rats
#13
Jingwen Liao, Yanyan Zhang, Fang Ye, Lin Zhang, Yu Chen, Fanxing Zeng, Lijun Shi
Accumulating evidence has shown that epigenetic regulation is involved in hypertension and aging. L-type voltage-gated Ca(2+) channels (LTCCs), the dominant channels in vascular myocytes, greatly contribute to arteriole contraction and blood pressure (BP) control. We investigated the dynamic changes and epigenetic regulation of LTCC in the mesenteric arteries of aging hypertensive rats. LTCC function was evaluated by using microvascular rings and whole-cell patch-clamp in the mesenteric arteries of male Wistar-Kyoto rats and spontaneously hypertensive rats at established hypertension (3 month old) and an aging stage (16 month old), respectively...
November 24, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27881786/neuronal-dysfunction-in-ipsc-derived-medium-spiny-neurons-from-chorea-acanthocytosis-patients-is-reversed-by-src-kinase-inhibition-and-f-actin-stabilization
#14
Nancy Stanslowsky, Peter Reinhardt, Hannes Glass, Norman Kalmbach, Maximilian Naujock, Niko Hensel, Verena Lübben, Arun Pal, Anna Venneri, Francesca Lupo, Lucia De Franceschi, Peter Claus, Jared Sterneckert, Alexander Storch, Andreas Hermann, Florian Wegner
: Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell membrane disturbances based on depolymerized cortical actin and an elevated Lyn kinase activity in erythrocytes from ChAc patients were identified. How this contributes to the mechanism of neurodegeneration is still unknown. To gain insight into the pathophysiology, we established a ChAc patient-derived induced pluripotent stem cell model and an efficient differentiation protocol providing a large population of human striatal medium spiny neurons (MSNs), the main target of neurodegeneration in ChAc...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27872583/ablation-of-sphingosine-1-phosphate-receptor-subtype-3-impairs-hippocampal-neuron-excitability-in-vitro-and-spatial-working-memory-in-vivo
#15
Daniela Weth-Malsch, Michiel Langeslag, Dimitra Beroukas, Luca Zangrandi, Iris Kastenberger, Serena Quarta, Philipp Malsch, Theodora Kalpachidou, Christoph Schwarzer, Richard L Proia, Rainer V Haberberger, Michaela Kress
Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P) within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P3) in vivo and in vitro with a special focus on the hippocampus...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27872281/interactions-of-divalent-cations-with-calcium-binding-sites-of-bk-channels-reveal-independent-motions-within-the-gating-ring
#16
Pablo Miranda, Teresa Giraldez, Miguel Holmgren
Large-conductance voltage- and calcium-activated K(+) (BK) channels are key physiological players in muscle, nerve, and endocrine function by integrating intracellular Ca(2+) and membrane voltage signals. The open probability of BK channels is regulated by the intracellular concentration of divalent cations sensed by a large structure in the BK channel called the "gating ring," which is formed by four tandems of regulator of conductance for K(+) (RCK1 and RCK2) domains. In contrast to Ca(2+) that binds to both RCK domains, Mg(2+), Cd(2+), or Ba(2+) interact preferentially with either one or the other...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27869701/the-role-of-individual-disulfide-bonds-of-%C3%AE-conotoxin-giiia-in-the-inhibition-of-nav1-4
#17
Penggang Han, Kang Wang, Xiandong Dai, Ying Cao, Shangyi Liu, Hui Jiang, Chongxu Fan, Wenjian Wu, Jisheng Chen
μ-Conotoxin GIIIA, a peptide toxin isolated from Conus geographus, preferentially blocks the skeletal muscle sodium channel NaV1.4. GIIIA folds compactly to a pyramidal structure stabilized by three disulfide bonds. To assess the contributions of individual disulfide bonds of GIIIA to the blockade of NaV1.4, seven disulfide-deficient analogues were prepared and characterized, each with one, two, or three pairs of disulfide-bonded Cys residues replaced with Ala. The inhibitory potency of the analogues against NaV1...
November 18, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27864268/de-novo-gabrg2-mutations-associated-with-epileptic-encephalopathies
#18
Dingding Shen, Ciria C Hernandez, Wangzhen Shen, Ningning Hu, Annapurna Poduri, Beth Shiedley, Alex Rotenberg, Alexandre N Datta, Steffen Leiz, Steffi Patzer, Rainer Boor, Kerri Ramsey, Ethan Goldberg, Ingo Helbig, Xilma R Ortiz-Gonzalez, Johannes R Lemke, Eric D Marsh, Robert L Macdonald
Epileptic encephalopathies are a devastating group of severe childhood onset epilepsies with medication-resistant seizures and poor developmental outcomes. Many epileptic encephalopathies have a genetic aetiology and are often associated with de novo mutations in genes mediating synaptic transmission, including GABAA receptor subunit genes. Recently, we performed next generation sequencing on patients with a spectrum of epileptic encephalopathy phenotypes, and we identified five novel (A106T, I107T, P282S, R323W and F343L) and one known (R323Q) de novo GABRG2 pathogenic variants (mutations) in eight patients...
November 17, 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27862283/footshock-induced-plasticity-of-gabab-signalling-in-the-lateral-habenula-requires-dopamine-and-glucocorticoid-receptors
#19
Salvatore Lecca, Massimo Trusel, Manuel Mameli
The activity of lateral habenula (LHb) represents a substrate for the encoding of negative-valenced events. The exposure to aversive stimuli in naïve mice is sufficient to trigger a reduction in GABAB -mediated signaling in the LHb. This is ultimately instrumental for the hyperactivity of LHb neurons and for the establishment of depressive-like phenotypes. However, the mechanisms responsible for the induction of this aversion-driven plasticity are missing. Using ex-vivo patch-clamp recordings in slices, here we show that exposing mice to a series of inescapable footshocks (FsE) rapidly reduces baclofen-mediated GABAB currents in the LHb...
November 10, 2016: Synapse
https://www.readbyqxmd.com/read/27861889/margatoxin-bound-quantum-dots-as-a-novel-inhibitor-of-the-voltage-gated-ion-channel-kv1-3
#20
Austin B Schwartz, Anshika Kapur, Wentao Wang, Zhenbo Huang, Erminia Fardone, Goutam Palui, Hedi Mattoussi, Debra Ann Fadool
Venom-derived ion channel inhibitors have strong channel selectivity, potency, and stability; however, tracking delivery to their target can be challenging. Herein, we utilized luminescent quantum dots (QDs) conjugated to margatoxin (MgTx) as a traceable vehicle to target a voltage-dependent potassium channel, Kv1.3, which has a select distribution and well characterized role in immunity, glucose metabolism, and sensory ability. We screened both unconjugated (MgTx) and conjugated MgTx (QD-MgTx) for their ability to inhibit Shaker channels Kv1...
November 8, 2016: Journal of Neurochemistry
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