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https://www.readbyqxmd.com/read/28924052/role-of-the-endothelial-caveolae-microdomain-in-shear-stress-mediated-coronary-vasorelaxation
#1
Tong Lu, Xiao-Li Wang, Qiang Chai, Xiaojing Sun, Gary C Sieck, Zvonimir S Katusic, Hon-Chi Lee
In this study, we determined the role of caveolae and the ionic mechanisms that mediate shear stress-mediated vasodilation (SSD). We found that both TRPV4 and SK channels are targeted to caveolae in freshly isolated bovine coronary endothelial cells (BCECs) and that TRPV4 and KCa2.3 (SK3) channels are co-immunoprecipitated by anti-caveolin-1 antibodies. Acute exposure of BCECs seeded in a capillary tube to 10 dynes/cm2 of SS resulted in activation of TRPV4 and SK currents. However, after incubation with HC067047 (TRPV4 inhibitor) SK currents could no longer be activated by SS, suggesting SK channel activation by SS was mediated through TRPV4...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28902181/platelet-derived-growth-factor-receptor-alpha-positive-cells-a-new-cell-type-in-the-human-ureteropelvic-junction
#2
Manuela Hunziker, Anne-Marie O'Donnell, Prem Puri
BACKGROUND: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis. Normal ureteral motility requires coordinated interaction between neurons, smooth muscle cells (SMCs), and interstitial Cajal-like cells (IC-LCs). Recently, a new type of interstitial cell, platelet-derived growth factor receptor α-positive (PDGFRα(+)) cells, was discovered in the gastrointestinal tract and bladder.MethodsWe used immunohistochemistry to study PDGFRα protein distribution in normal human UPJ and congenital UPJ obstruction...
September 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28886082/haloperidol-induces-pharmacoepigenetic-response-by-modulating-mirna-expression-global-dna-methylation-and-expression-profiles-of-methylation-maintenance-genes-and-genes-involved-in-neurotransmission-in-neuronal-cells
#3
Babu Swathy, Moinak Banerjee
INTRODUCTION: Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. METHODS: SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28884460/potassium-channels-a-potential-therapeutic-target-for-parkinson-s-disease
#4
REVIEW
Xiaoyan Chen, Bao Xue, Jun Wang, Haixia Liu, Limin Shi, Junxia Xie
The pathogenesis of the second major neurodegenerative disorder, Parkinson's disease (PD), is closely associated with the dysfunction of potassium (K(+)) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K(+) channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K(+) channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum...
September 7, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28878623/mechanisms-of-spontaneous-climbing-fiber-discharge-evoked-pauses-and-output-modulation-of-cerebellar-purkinje-cell-in-mice
#5
Xian-Hua Jin, Hong-Wei Wang, Xin-Yuan Zhang, Chun-Ping Chu, Yuan-Zhe Jin, Song-Biao Cui, De-Lai Qiu
Climbing fiber (CF) afferents modulate the frequency and patterns of cerebellar Purkinje cell (PC) simple spike (SS) activity, but its mechanism is unclear. In the present study, we investigated the mechanisms of spontaneous CF discharge-evoked pauses and the output modulation of cerebellar PCs in urethane-anesthetized mice using in vivo whole-cell recording techniques and pharmacological methods. Under voltage-clamp recording conditions, spontaneous CF discharge evoked strong inward currents followed by small conductance calcium-activated potassium (SK) channels that mediated outward currents...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28858616/inferior-olivary-tmem16b-mediates-cerebellar-motor-learning
#6
Yang Zhang, Zhushan Zhang, Shaohua Xiao, Jason Tien, Son Le, Trieu Le, Lily Y Jan, Huanghe Yang
Ca(2+)-activated ion channels shape membrane excitability and Ca(2+) dynamics in response to cytoplasmic Ca(2+) elevation. Compared to the Ca(2+)-activated K(+) channels, known as BK and SK channels, the physiological importance of Ca(2+)-activated Cl(-) channels (CaCCs) in neurons has been largely overlooked. Here we report that CaCCs coexist with BK and SK channels in inferior olivary (IO) neurons that send climbing fibers to innervate cerebellar Purkinje cells for the control of motor learning and timing...
August 30, 2017: Neuron
https://www.readbyqxmd.com/read/28818302/mitochondrial-ca-2-activated-k-channels-and-their-role-in-cell-life-and-death-pathways
#7
REVIEW
Inge E Krabbendam, Birgit Honrath, Carsten Culmsee, Amalia M Dolga
Ca(2+)-activated K(+) channels (KCa) are expressed at the plasma membrane and in cellular organelles. Expression of all KCa channel subtypes (BK, IK and SK) has been detected at the inner mitochondrial membrane of several cell types. Primary functions of these mitochondrial KCa channels include the regulation of mitochondrial ROS production, maintenance of the mitochondrial membrane potential and preservation of mitochondrial calcium homeostasis. These channels are therefore thought to contribute to cellular protection against oxidative stress through mitochondrial mechanisms of preconditioning...
July 22, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28790888/amyloid-%C3%AE-1-42-a%C3%AE-1-42-induces-the-cdk2-mediated-phosphorylation-of-tau-through-the-activation-of-the-mtorc1-signaling-pathway-while-promoting-neuronal-cell-death
#8
Ki Hoon Lee, Sei-Jung Lee, Hyun Jik Lee, Gee Euhn Choi, Young Hyun Jung, Dah Ihm Kim, Amr Ahmed Gabr, Jung Min Ryu, Ho Jae Han
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment and memory loss. Amyloid β1-42 (Aβ) and hyper-phosphorylation of microtubule-associated protein tau have been considered as major histological features in AD. However, the mechanism of how Aβ induces the hyper-phosphorylation of tau remains to be clarified. In the present study, we investigated the underlying cellular mechanisms of Aβ with regard to the cell cycle regulatory protein-mediated phosphorylation of tau in promoting neuronal cell death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28738160/atrial-selective-k-channel-blockers-potential-antiarrhythmic-drugs-in-atrial-fibrillation
#9
Ursula Ravens
In the wake of demographic change in Western countries atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. In this lecture, I will address drugs acting on potassium (K+) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles...
July 24, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28714070/a-reduction-in-sk-channels-contributes-to-increased-activity-of-hypothalamic-magnocellular-neurons-during-heart-failure
#10
H C Ferreira-Neto, V Biancardi, J E Stern
Small conductance Ca(2+) -activated K(+) channels (SK) play an important role in regulating MNCs activity and hormone release from the posterior pituitary. Moreover, an enhanced SK activity contributes to MNCs' adaptive responses to a physiological challenge, such as lactation. Still, whether changes in SK function/expression contribute to exacerbated MNCs activity during diseases like heart failure (HF), remains unknown. Here, we used a combination of patch-clamp electrophysiology, confocal Ca(2+) imaging and molecular biology in a rat model of ischemic HF...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28701955/therapeutic-properties-of-bioactive-compounds-from-different-honeybee-products
#11
REVIEW
Laura Cornara, Marco Biagi, Jianbo Xiao, Bruno Burlando
Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28701749/calcium-activated-sk-channels-control-firing-regularity-by-modulating-sodium-channel-availability-in-midbrain-dopamine-neurons
#12
Rajeshwari Iyer, Mark A Ungless, Aldo A Faisal
Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area regulate behaviours such as reward-related learning, and motor control. Dysfunction of these neurons is implicated in Schizophrenia, addiction to drugs, and Parkinson's disease. While some dopamine neurons fire single spikes at regular intervals, others fire irregular single spikes interspersed with bursts. Pharmacological inhibition of calcium-activated potassium (SK) channels increases the variability in their firing pattern, sometimes also increasing the number of spikes fired in bursts, indicating that SK channels play an important role in maintaining dopamine neuron firing regularity and burst firing...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28682239/physiological-and-pathophysiological-control-of-synaptic-glun2b-nmda-receptors-by-the-c-terminal-domain-of-amyloid-precursor-protein
#13
Paula A Pousinha, Xavier Mouska, Elisabeth F Raymond, Carole Gwizdek, Gihen Dhib, Gwenola Poupon, Laure-Emmanuelle Zaragosi, Camilla Giudici, Ingrid Bethus, Emilie Pacary, Michael Willem, Hélène Marie
The amyloid precursor protein (APP) harbors physiological roles at synapses and is central to Alzheimer's disease (AD) pathogenesis. Evidence suggests that APP intracellular domain (AICD) could regulate synapse function, but the underlying molecular mechanisms remain unknown. We addressed AICD actions at synapses, per se, combining in vivo AICD expression, ex vivo AICD delivery or APP knock-down by in utero electroporation of shRNAs with whole-cell electrophysiology. We report a critical physiological role of AICD in controlling GluN2B-containing NMDA receptors (NMDARs) at immature excitatory synapses, via a transcription-dependent mechanism...
July 6, 2017: ELife
https://www.readbyqxmd.com/read/28613412/myoendothelial-coupling-through-cx40-contributes-to-edh-induced-vasodilation-in-murine-renal-arteries-evidence-from-experiments-and-modelling
#14
Jens Christian Brasen, Cor de Wit, Charlotte Mehlin Sorensen
Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles but the exact mechanisms are still unknown AIM: to investigate the role of vascular gap junctions and potassium channels in the renal endothelial derived hyperpolarization. METHODS: in interlobar arteries from wild-type and connexin40 knock-out mice we assessed the role of calcium activated small (SK) and intermediate (IK) conductance potassium channels...
June 14, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28596131/control-of-anterior-pituitary-cell-excitability-by-calcium-activated-potassium-channels
#15
REVIEW
Michael J Shipston
In anterior pituitary endocrine cells, large (BK), small (SK) and intermediate (IK) conductance calcium activated potassium channels are key determinants in shaping cellular excitability in a cell type- and context-specific manner. Indeed, these channels are targeted by multiple signaling pathways that stimulate or inhibit cellular excitability. BK channels can, paradoxically, both promote electrical bursting as well as terminate bursting and spiking dependent upon intrinsic BK channel properties and proximity to voltage gated calcium channels in somatotrophs, lactotrophs and corticotrophs...
June 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28591834/cholinergic-grb2-associated-binding-protein-1-regulates-cognitive-function
#16
Nan-Nan Lu, Chao Tan, Ning-He Sun, Ling-Xiao Shao, Xiu-Xiu Liu, Yin-Ping Gao, Rong-Rong Tao, Quan Jiang, Cheng-Kun Wang, Ji-Yun Huang, Kui Zhao, Guang-Fa Wang, Zhi-Rong Liu, Kohji Fukunaga, Ying-Mei Lu, Feng Han
Grb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer's disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons...
June 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28550095/small-conductance-calcium-activated-potassium-current-in-normal-rabbit-cardiac-purkinje-cells
#17
Thomas A Reher, Zhuo Wang, Chia-Hsiang Hsueh, Po-Cheng Chang, Zhenwei Pan, Mohineesh Kumar, Jheel Patel, Jian Tan, Changyu Shen, Zhenhui Chen, Michael C Fishbein, Michael Rubart, Penelope Boyden, Peng-Sheng Chen
BACKGROUND: Purkinje cells (PCs) are important in cardiac arrhythmogenesis. Whether small-conductance calcium-activated potassium (SK) channels are present in PCs remains unclear. We tested the hypotheses that subtype 2 SK (SK2) channel proteins and apamin-sensitive SK currents are abundantly present in PCs. METHODS AND RESULTS: We studied 25 normal rabbit ventricles, including 13 patch-clamp studies, 4 for Western blotting, and 8 for immunohistochemical staining...
May 26, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28511953/small-conductance-ca-2-activated-k-channels-in-the-plasma-membrane-mitochondria-and-the-er-pharmacology-and-implications-in-neuronal-diseases
#18
REVIEW
Birgit Honrath, Inge E Krabbendam, Carsten Culmsee, Amalia M Dolga
Ca(2+)-activated K(+) (KCa) channels regulate after-hyperpolarization in many types of neurons in the central and peripheral nervous system. Small conductance Ca(2+)-activated K(+) (KCa2/SK) channels, a subfamily of KCa channels, are widely expressed in the nervous system, and in the cardiovascular system. Voltage-independent SK channels are activated by alterations in intracellular Ca(2+) ([Ca(2+)]i) which facilitates the opening of these channels through binding of Ca(2+) to calmodulin that is constitutively bound to the SK2 C-terminus...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28502716/neuropeptides-predicted-from-the-transcriptome-analysis-of-the-gray-garden-slug-deroceras-reticulatum
#19
Seung-Joon Ahn, Ruth Martin, Sujaya Rao, Man-Yeon Choi
The gray garden slug, Deroceras reticulatum (Gastropoda: Pulmonata), is one of the most common terrestrial molluscs. Research for this slug has focused mainly on its ecology, biology, and management due to the severe damage it causes on a wide range of vegetables and field crops. However, little is known about neuropeptides and hormonal signalings. This study, therefore, aimed to establish the transcriptome of D. reticulatum and to identify a comprehensive repertoire of neuropeptides in this slug. Illumina high-throughput sequencing of the whole body transcriptome of D...
May 11, 2017: Peptides
https://www.readbyqxmd.com/read/28495974/long-term-depression-of-intrinsic-excitability-accompanied-by-synaptic-depression-in-cerebellar-purkinje-cells
#20
Hyun Geun Shim, Dong Cheol Jang, Jaegeon Lee, Geehoon Chung, Sukchan Lee, Yong Gyu Kim, Da Eun Jeon, Sang Jeong Kim
Long-term depression (LTD) at the parallel fiber (PF)-to-cerebellar Purkinje cell (PC) synapse is implicated in the output of PCs, the sole output of the cerebellar cortex. In addition to synaptic plasticity, intrinsic excitability is also one of the components that determines PC output. Although long-term potentiation of intrinsic excitability (LTP-IE) has been suggested, it has yet to be investigated how PF-PC LTD modifies intrinsic excitability of PCs. Here, we show that pairing of the PF and climbing fiber (CF) for PF-PC LTD induction evokes LTD-IE in cerebellar PCs from male C57BL/6 mice...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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