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https://www.readbyqxmd.com/read/28768770/nmda-receptors-mediate-leptin-signaling-and-regulate-potassium-channel-trafficking-in-pancreatic-%C3%AE-cells
#1
Yi Wu, Dale A Fortin, Veronica A Cochrane, Pei-Chun Chen, Show-Ling Shyng
NMDA receptors (NMDARs) are Ca2+-permeant, ligand-gated ion channels activated by the excitatory neurotransmitter glutamate and have well-characterized roles in the nervous system. The expression and function of NMDARs in pancreatic β cells, by contrast, are poorly understood. Here, we report a novel function of NMDARs in β-cells. Using a combination of biochemistry, electrophysiology, and imaging techniques we now show that NMDARs have a key role in mediating the effect of leptin to modulate β-cell electrical activity by promoting AMP-activated protein kinase (AMPK)-dependent trafficking of KATP and Kv2...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28706455/escitalopram-a-selective-serotonin-reuptake-inhibitor-inhibits-voltage-dependent-k-channels-in-coronary-arterial-smooth-muscle-cells
#2
Han Sol Kim, Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Grace Choi, Dae-Sung Lee, Won Sun Park
We investigated the inhibitory effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K(+) (Kv) channels in freshly separated from rabbit coronary arterial smooth muscle cells. The application of escitalopram rapidly inhibited vascular Kv channels. Kv currents were progressively inhibited by an increase in the concentrations of escitalopram, suggesting that escitalopram inhibited vascular Kv currents in a concentration-dependent manner. The IC50 value and Hill coefficient for escitalopram-induced inhibition of Kv channels were 9...
July 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28697955/nesfatin-1-inhibits-voltage-gated-k-channels-in-pancreatic-beta-cells
#3
Yuko Maejima, Shoichiro Horita, Daisuke Kobayashi, Miho Aoki, Rie O'hashi, Ryota Imai, Kazuho Sakamoto, Masatomo Mori, Katsuya Takasu, Kazuma Ogawa, Seiichi Takenoshita, Songji Zhao, Akihiro Hazama, Kenju Shimomura
The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/nesfatin-1-containing neurons are distributed in the brain regions involved in feeding regulation. In spite of the growing knowledge of its physiological functions through extensive studies, its molecular mechanism of reaction, including its receptor, remains unknown. NUCB2/nesfatin-1 is also involved in various peripheral regulations, including glucose homeostasis. In pancreatic beta-cells, NUCB2/nesfatin-1 is reported to enhance glucose-stimulated insulin secretion (GSIS) but its exact mechanism remains unknown...
July 8, 2017: Peptides
https://www.readbyqxmd.com/read/28668511/voltage-sensitive-potassium-channels-expressed-after-20-hydroxyecdysone-treatment-of-a-mosquito-cell-line
#4
Lacey J Jenson, Baonan Sun, Jeffrey R Bloomquist
The goal of this research was to express receptors and ion channels in hormone-treated insect cell lines. Treatment of Anopheles gambiae Sua1B cells with 20-hydroxyecdysone showed an inhibition of cell growth over a time course of three days, with no change in cellular morphology. The effect of 20-hydroxyecdysone was enhanced in the presence of the potassium channel blocker 4-aminopyridine, but not tetraethylammonium. Concentration-response curves of 4-aminopyridine in the presence of 42 μM (1 mg/ml) 20-hydroxyecdysone showed similar IC50 values (6-10 μM) across 3 day exposures...
August 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28658141/pharmacogenetic-and-case-control-study-on-potassium-channel-related-gene-variants-and-genetic-generalized-epilepsy
#5
Jian Qu, Shao-Hua Lu, Zhi-Li Lu, Ping Xu, Da-Xiong Xiang, Qiang Qu
Potassium channels are the targets of antiepileptic drugs (AEDs), which play important roles in the etiology of epilepsy. KCNA1 and KCNA2 encode mammalian Kv1.1 and Kv1.2 channels, which are essential roles in the initiation and shaping of action potentials. KCNV2 encodes Kv8.2, which is a regional overlap with Kv2 subunits as functional heterotetramers. In our study, we aim to investigate whether variants of KCNA1, KCNA2, and KCNV2 genes influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of AEDs...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28607108/kv2-1-clustering-contributes-to-insulin-exocytosis-and-rescues-human-%C3%AE-cell-dysfunction
#6
Jianyang Fu, Xiaoqing Dai, Gregory Plummer, Kunimasa Suzuki, Austin Bautista, John M Githaka, Laura Senior, Mette Jensen, Dafna Greitzer-Antes, Jocelyn E Manning Fox, Herbert Y Gaisano, Christopher B Newgard, Nicolas Touret, Patrick E MacDonald
Insulin exocytosis is regulated by ion channels that control excitability and Ca(2+) influx. Channels also play an increasingly appreciated role in microdomain structure. In this study, we examine the mechanism by which the voltage-dependent K(+) (Kv) channel Kv2.1 (KCNB1) facilitates depolarization-induced exocytosis in INS 832/13 cells and β-cells from human donors with and without type 2 diabetes (T2D). We find that Kv2.1, but not Kv2.2 (KCNB2), forms clusters of 6-12 tetrameric channels at the plasma membrane and facilitates insulin exocytosis...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28603004/ion-channel-signaling-influences-cellular-proliferation-and-phagocyte-activity-during-axolotl-tail-regeneration
#7
Brandon M Franklin, S Randal Voss, Jeffrey L Osborn
Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, KV2.1, KV2.2, L-type CaV channels and H/K ATPases) or completely (GlyR, GABAAR, KV1.5 and SERCA pumps) inhibited tail regeneration...
August 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28504671/reduced-sensory-synaptic-excitation-impairs-motor-neuron-function-via-kv2-1-in-spinal-muscular-atrophy
#8
Emily V Fletcher, Christian M Simon, John G Pagiazitis, Joshua I Chalif, Aleksandra Vukojicic, Estelle Drobac, Xiaojian Wang, George Z Mentis
Behavioral deficits in neurodegenerative diseases are often attributed to the selective dysfunction of vulnerable neurons via cell-autonomous mechanisms. Although vulnerable neurons are embedded in neuronal circuits, the contributions of their synaptic partners to disease process are largely unknown. Here we show that, in a mouse model of spinal muscular atrophy (SMA), a reduction in proprioceptive synaptic drive leads to motor neuron dysfunction and motor behavior impairments. In SMA mice or after the blockade of proprioceptive synaptic transmission, we observed a decrease in the motor neuron firing that could be explained by the reduction in the expression of the potassium channel Kv2...
July 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28495226/a-gas-flow-model-for-layered-landfills-with-vertical-extraction-wells
#9
Shi-Jin Feng, Qi-Teng Zheng, Hai-Jian Xie
This paper developed a two-dimensional axisymmetric analytical model for layered landfills with vertical wells. The model uses a horizontal layered structure to describe the waste non-homogeneity with depth in gas generation, permeability and temperature. The governing equations in the cylindrical coordinate system were transformed to dimensionless forms and solved using a method of eigenfunction expansion. After verification, the effects of different well boundary conditions and gas extraction systems on recovery efficiency were investigated...
May 8, 2017: Waste Management
https://www.readbyqxmd.com/read/28483976/targeting-a-potassium-channel-syntaxin-interaction-ameliorates-cell-death-in-ischemic-stroke
#10
Chung-Yang Yeh, Ashlyn M Bulas, Aubin Moutal, Jami L Saloman, Karen A Hartnett, Charles T Anderson, Thanos Tzounopoulos, Dandan Sun, Rajesh Khanna, Elias Aizenman
The voltage-gated K(+) channel Kv2.1 has been intimately linked with neuronal apoptosis. After ischemic, oxidative, or inflammatory insults, Kv2.1 mediates a pronounced, delayed enhancement of K(+) efflux, generating an optimal intracellular environment for caspase and nuclease activity, key components of programmed cell death. This apoptosis-enabling mechanism is initiated via Zn(2+)-dependent dual phosphorylation of Kv2.1, increasing the interaction between the channel's intracellular C-terminus domain and the SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) protein syntaxin 1A...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28461216/disruption-of-kv2-1-somato-dendritic-clusters-prevents-the-apoptogenic-increase-of-potassium-currents
#11
Jason A Justice, Anthony J Schulien, Kai He, Karen A Hartnett, Elias Aizenman, Niyathi H Shah
As the predominant mediator of the delayed rectifier current, KV2.1 is an important regulator of neuronal excitability. KV2.1, however, also plays a well-established role in apoptotic cell death. Apoptogenic stimuli induce syntaxin-dependent trafficking of KV2.1, resulting in an augmented delayed rectifier current that acts as a conduit for K(+) efflux required for pro-apoptotic protease/nuclease activation. Recent evidence suggests that KV2.1 somato-dendritic clusters regulate the formation of endoplasmic reticulum-plasma membrane junctions that function as scaffolding sites for plasma membrane trafficking of ion channels, including KV2...
April 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/28391996/molecular-mechanisms-underlying-pimaric-acid-induced-modulation-of-voltage-gated-k-channels
#12
Kazuho Sakamoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Katsuhiko Muraki, Yuji Imaizumi
Voltage-gated K(+) (KV) channels, which control firing and shape of action potentials in excitable cells, are supposed to be potential therapeutic targets in many types of diseases. Pimaric acid (PiMA) is a unique opener of large conductance Ca(2+)-activated K(+) channel. Here, we report that PiMA modulates recombinant rodent KV channel activity. The enhancement was significant at low potentials (<0 mV) but not at more positive potentials. Application of PiMA significantly shifted the voltage-activation relationships (V1/2) of rodent KV1...
April 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28365825/inhibition-of-inwardly-rectifying-kir2-x-channels-by-the-novel-anti-cancer-agent-gambogic-acid-depends-on-both-pore-block-and-pip2-interference
#13
Daniel Scherer, Benedikt Schworm, Claudia Seyler, Panagiotis Xynogalos, Eberhard P Scholz, Dierk Thomas, Hugo A Katus, Edgar Zitron
The caged xanthone gambogic acid (GA) is a novel anti-cancer agent which exhibits anti-proliferative, anti-inflammatory and cytotoxic effects in many types of cancer tissues. In a recent phase IIa study, GA exhibits a favourable safety profile. However, limited data are available concerning its interaction with cardiac ion channels. Heteromeric assembly of Kir2.x channels underlies the cardiac inwardly rectifying IK1 current which is responsible for the stabilization of the diastolic resting membrane potential...
April 2, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#14
Timur A Mavlyutov, Erin M Baker, Tasher M Losenegger, Jaimie R Kim, Brian Torres, Miles L Epstein, Arnold E Ruoho
The membrane bound 223 amino acid Sigma-1 Receptor (S1R) serves as a molecular chaperone and functional regulator of many signaling proteins. Spinal cord motor neuron activation occurs, in part, via large ventral horn cholinergic synapses called C-boutons/C-terminals. Chronic excitation of motor neurons and alterations in C-terminals has been associated with Amyotrophic Lateral Sclerosis (ALS ). The S1R has an important role in regulating motor neuron function. High levels of the S1R are localized in postsynaptic endoplasmic reticulum (ER) subsurface cisternae within 10-20 nm of the plasma membrane that contain muscarinic type 2 acetylcholine receptors (M2AChR), calcium activated potassium channels (Kv2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28280416/nortriptyline-a-tricyclic-antidepressant-inhibits-voltage-dependent-k-channels-in-coronary-arterial-smooth-muscle-cells
#15
Sung Eun Shin, Hongliang Li, Han Sol Kim, Hye Won Kim, Mi Seon Seo, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Il-Whan Choi, Young Min Bae, Won Sun Park
We demonstrated the effect of nortriptyline, a tricyclic antidepressant drug and serotonin reuptake inhibitor, on voltage-dependent K(+) (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Nortriptyline inhibited Kv currents in a concentration-dependent manner, with an apparent IC50 value of 2.86±0.52 µM and a Hill coefficient of 0.77±0.1. Although application of nortriptyline did not change the activation curve, nortriptyline shifted the inactivation current toward a more negative potential...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28260386/measurement-of-hanatoxin-induced-membrane-thinning-with-lamellar-x-ray-diffraction
#16
Meng-Hsuan Hsieh, Yu-Shuan Shiau, Horng-Huei Liou, U-Ser Jeng, Ming-Tao Lee, Kuo-Long Lou
Membrane perturbation induced by cysteine-rich peptides is a crucial biological phenomenon but scarcely investigated, in particular with effective biophysical-chemical methodologies. Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, works as an inhibitor of drk1 (Kv2.1) channels, most likely by interacting with the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage sensor was proposed to be deeply embedded within the bilayer. To see how HaTx interacts with phospholipid bilayers, we observe the toxin-induced perturbation on POPC/DOPG-membranes through measurements of the change in membrane thickness...
March 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28247497/centipede-venom-peptide-ssmtx-i-with-two-intramolecular-disulfide-bonds-shows-analgesic-activities-in-animal-models
#17
Ying Wang, Xiaojie Li, Meifeng Yang, Chunyun Wu, Zhirong Zou, Jing Tang, Xinwang Yang
Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans...
May 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28143758/hanatoxin-inserts-into-phospholipid-membranes-without-pore-formation
#18
Kuo-Long Lou, Meng-Hsuan Hsieh, Wei-Jung Chen, Yu-Che Cheng, Jia-Nan Jian, Ming-Tao Lee, Tsang-Lang Lin, Yu-Shuan Shiau, Horng-Huei Liou
Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, functions as an inhibitor of Kv2.1 channels by interacting with phospholipids prior to affecting the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage-sensor is deeply embedded within the bilayer. To determine how HaTx interacts with phospholipid bilayers, in this study, we examined the toxin-induced partitioning of liposomal membranes. HPLC-results from high-speed spin-down vesicles with HaTx demonstrated direct binding...
May 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28139741/independent-movement-of-the-voltage-sensors-in-kv2-1-kv6-4-heterotetramers
#19
Elke Bocksteins, Dirk J Snyders, Miguel Holmgren
Heterotetramer voltage-gated K(+) (KV) channels KV2.1/KV6.4 display a gating charge-voltage (QV) distribution composed by two separate components. We use state dependent chemical accessibility to cysteines substituted in either KV2.1 or KV6.4 to assess the voltage sensor movements of each subunit. By comparing the voltage dependences of chemical modification and gating charge displacement, here we show that each gating charge component corresponds to a specific subunit forming the heterotetramer. The voltage sensors from KV6...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065942/neuregulin-1-erbb-module-in-c-bouton-synapses-on-somatic-motor-neurons-molecular-compartmentation-and-response-to-peripheral-nerve-injury
#20
Anna Casanovas, Sara Salvany, Víctor Lahoz, Olga Tarabal, Lídia Piedrafita, Raimundo Sabater, Sara Hernández, Jordi Calderó, Josep E Esquerda
The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown...
January 9, 2017: Scientific Reports
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