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Kv2.1

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https://www.readbyqxmd.com/read/29773183/cytosolic-increased-labile-zn-2-contributes-to-arrhythmogenic-action-potentials-in-left-ventricular-cardiomyocytes-through-protein-thiol-oxidation-and-cellular-atp-depletion
#1
Sinan Degirmenci, Yusuf Olgar, Aysegul Durak, Erkan Tuncay, Belma Turan
Intracellular labile (free) Zn2+ -level ([Zn2+ ]i ) is low and increases markedly under pathophysiological conditions in cardiomyocytes. High [Zn2+ ]i is associated with alterations in excitability and ionic-conductances while exact mechanisms are not clarified yet. Therefore, we examined the elevated-[Zn2+ ]i on some sarcolemmal ionic-mechanisms, which can mediate cardiomyocyte dysfunction. High-[Zn2+ ]i induced significant changes in action potential (AP) parameters, including depolarization in resting membrane-potential and prolongations in AP-repolarizing phases...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29752209/blockade-of-voltage-dependent-k-current-in-rabbit-coronary-arterial-smooth-muscle-cells-by-the-tricyclic-antidepressant-clomipramine
#2
Hongliang Li, Sung Eun Shin, Jin Ryeol An, Mi Seon Seo, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Dae-Sung Lee, Mi-Jin Yim, Jeong Min Lee, Grace Choi, Il-Whan Choi, Won Sun Park
We investigated the effect of the tricyclic antidepressant clomipramine on voltage-dependent K+ (Kv) channels in native rabbit coronary arterial smooth muscle cells. Our results showed that clomipramine inhibited vascular Kv channels in a concentration-dependent manner, with an IC50 value of 8.61 ± 4.86 μM and a Hill coefficient (n) of 0.58 ± 0.07. The application of 10 μM clomipramine did not affect the activation curves of the Kv channels; however, the inactivation curves of the Kv channels were shifted toward a more negative potential...
April 27, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29720558/two-distinct-secretory-pathways-for-differential-kv2-1-localization-in-neurons
#3
Brian Christopher Lim, Cheng-Hsin Liu
No abstract text is available yet for this article.
May 2, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29703946/cleavage-of-potassium-channel-kv2-1-by-bace2-reduces-neuronal-apoptosis
#4
Fuchen Liu, Yun Zhang, Zonglai Liang, Qianwen Sun, Heng Liu, Juan Zhao, Jingwen Xu, Jinfan Zheng, Yan Yun, Xiao Yu, Weihong Song, Xiulian Sun
Potassium channel Kv2.1 regulates potassium current in cortical neurons and potassium efflux is necessary for cell apoptosis. As a major component of delayed rectifier current potassium channels, Kv2.1 forms clusters in the membrane of hippocampal neurons. BACE2 is an aspartyl protease to cleave APP to prevent the generation of Aβ, a central component of neuritic plaques in Alzheimer's brain. We now identified Kv2.1 as a novel substrate of BACE2. We found that BACE2 cleaved Kv2.1 at Thr376, Ala717, and Ser769 sites and disrupted Kv2...
April 27, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29550337/paeonol-promotes-hippocampal-synaptic-transmission-the-role-of-the-kv2-1-potassium-channel
#5
Chin-Tsang Yang, Guan-Ling Lu, Sheng-Feng Hsu, Iona MacDonald, Lih-Chu Chiou, Shih-Ya Hung, Yi-Hung Chen
Paeonol is a major constituent of the Chinese herb Moutan cortex radices. Recent studies report that paeonol has neuroprotective effects and improves impaired learning and memory. However, its underlying mechanisms by which paeonol contributes to synaptic transmission remain unclear. In this study, we found that paeonol increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs), but had no effect on the amplitude in rat hippocampal CA1 neurons...
May 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29549124/k-v-2-1-clusters-on-%C3%AE-cell-plasma-membrane-act-as-reservoirs-that-replenish-pools-of-newcomer-insulin-granule-through-their-interaction-with-syntaxin-3
#6
Dafna Greitzer-Antes, Li Xie, Tairan Qin, Huanli Xie, Dan Zhu, Subhankar Dolai, Tao Liang, Fei Kang, Alexandre B Hardy, Yan He, Youhou Kang, Herbert Y Gaisano
The voltage-dependent K+ (Kv ) channel Kv 2.1 is a major delayed rectifier in many secretory cells, including pancreatic β cells. In addition, Kv 2.1 has a direct role in exocytosis at an undefined step, involving SNARE proteins, that is independent of its ion-conducting pore function. Here, we elucidated the precise step in exocytosis. We previously reported that syntaxin-3 (Syn-3) is the key syntaxin that mediates exocytosis of newcomer secretory granules that spend minimal residence time on the plasma membrane before fusion...
May 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29483285/heteromeric-k-v-2-k-v-8-2-channels-mediate-delayed-rectifier-potassium-currents-in-primate-photoreceptors
#7
Jacqueline Gayet-Primo, Daniel B Yaeger, Roupen A Khanjian, Teresa Puthussery
Silent voltage-gated potassium channel subunits (KV S) interact selectively with members of the KV 2 channel family to modify their functional properties. The localization and functional roles of these silent subunits remain poorly understood. Mutations in the KV S subunit, KV 8.2 ( KCNV2 ), lead to severe visual impairment in humans, but the basis of these deficits remains unclear. Here, we examined the localization, native interactions, and functional properties of KV 8.2-containing channels in mouse, macaque, and human photoreceptors of either sex...
April 4, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29403353/kv2-ion-channels-determine-the-expression-and-localization-of-the-associated-amigo-1-cell-adhesion-molecule-in-adult-brain-neurons
#8
Hannah I Bishop, Melanie M Cobb, Michael Kirmiz, Laxmi K Parajuli, Danielle Mandikian, Ashleigh M Philp, Mikhail Melnik, Juha Kuja-Panula, Heikki Rauvala, Ryuichi Shigemoto, Karl D Murray, James S Trimmer
Voltage-gated K+ (Kv) channels play important roles in regulating neuronal excitability. Kv channels comprise four principal α subunits, and transmembrane and/or cytoplasmic auxiliary subunits that modify diverse aspects of channel function. AMIGO-1, which mediates homophilic cell adhesion underlying neurite outgrowth and fasciculation during development, has recently been shown to be an auxiliary subunit of adult brain Kv2.1-containing Kv channels. We show that AMIGO-1 is extensively colocalized with both Kv2...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29379118/regulation-of-kv2-1-channel-inactivation-by-phosphatidylinositol-4-5-bisphosphate
#9
Mayra Delgado-Ramírez, José J De Jesús-Pérez, Iván A Aréchiga-Figueroa, Jorge Arreola, Scott K Adney, Carlos A Villalba-Galea, Diomedes E Logothetis, Aldo A Rodríguez-Menchaca
Phosphatidylinositol 4,5-bisphosphate (PIP2 ) is a membrane phospholipid that regulates the function of multiple ion channels, including some members of the voltage-gated potassium (Kv) channel superfamily. The PIP2 sensitivity of Kv channels is well established for all five members of the Kv7 family and for Kv1.2 channels; however, regulation of other Kv channels by PIP2 remains unclear. Here, we investigate the effects of PIP2 on Kv2.1 channels by applying exogenous PIP2 to the cytoplasmic face of excised membrane patches, activating muscarinic receptors (M1R), or depleting endogenous PIP2 using a rapamycin-translocated 5-phosphatase (FKBP-Inp54p)...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29297590/involvement-of-the-delayed-rectifier-outward-potassium-channel-kv2-1-in-methamphetamine-induced-neuronal-apoptosis-via-the-p38-mitogen-activated-protein-kinase-signaling-pathway
#10
Jingying Zhu, Songsong Zang, Xufeng Chen, Lei Jiang, Aihua Gu, Jie Cheng, Li Zhang, Jun Wang, Hang Xiao
Methamphetamine (Meth) is an illicit psychostimulant with high abuse potential and severe neurotoxicity. Recent studies have shown that dysfunctions in learning and memory induced by Meth may partially reveal the mechanisms of neuronal channelopathies. Kv2.1, the primary delayed rectifying potassium channel in neurons, is responsible for mediating apoptotic current surge. However, whether Kv2.1 is involved in Meth-mediated neural injury remains unknown. In the present study, the treatment of primary cultured hippocampal neurons with Meth indicated that Meth induced a time- and dose-dependent augmentation of Kv2...
May 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29183608/n-mono-and-n-n-diacyl-derivatives-of-benzyl-and-arylhydrazines-as-contact-insecticides-against-adult-anopheles-gambiae
#11
Joseph S Clements, Rafique Islam, Baonan Sun, Fan Tong, Aaron D Gross, Jeffrey R Bloomquist, Paul R Carlier
New public health insecticides are urgently required to prevent the spread of vector-borne disease. With the goal of identifying new K+ -channel-directed mosquitocides, analogs of the RH-5849 family of diacyl t-butylhydrazines were synthesized and tested for topical toxicity against adult Anopheles gambiae, the African vector of malaria. In total, 80N'-monoacyl and N, N'-diacyl derivatives of benzyl- and arylhydrazines were prepared. Three compounds (2bo, 2kb, 3ab) were identified that were more toxic than RH-5849 and RH-1266...
November 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29134326/inhibition-of-the-voltage-dependent-k-current-by-the-tricyclic-antidepressant-desipramine-in-rabbit-coronary-arterial-smooth-muscle-cells
#12
Sung Eun Shin, Hongliang Li, Jin Ryeol An, Mi Seon Seo, Sung Hun Na, Won-Kyo Jung, Amy L Firth, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Won Sun Park
We describe the effect of a tricyclic antidepressant drug desipramine on voltage-dependent K(+) (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells using a conventional whole-cell patch clamp technique. Application of desipramine rapidly decreased the Kv current amplitude in a concentration-dependent manner, with an IC50 value of 5.91 ± 0.18 μM and a Hill coefficient of 0.61 ± 0.09. The steady-state inactivation curves of the Kv channels were not affected by desipramine. However, desipramine shifted the steady-state inactivation curves toward a more negative potential...
November 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29128793/phytochemicals-genistein-and-capsaicin-modulate-kv2-1-channel-gating
#13
Iván A Aréchiga-Figueroa, Rita Morán-Zendejas, Mayra Delgado-Ramírez, Aldo A Rodríguez-Menchaca
BACKGROUND: Phytochemicals are a large group of plant-derived compounds that have a broad range of pharmacological effects. Some of these effects are derived from their action on transport proteins, including ion channels. The present study investigates the effects of the phytochemicals genistein and capsaicin on voltage-gated potassium Kv2.1 channels. METHODS: The whole-cell patch clamp technique was used to explore the regulation of Kv2.1 channels expressed in HEK293 cells by genistein and capsaicin...
December 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29042434/trafficking-of-kv2-1-channels-to-the-axon-initial-segment-by-a-novel-nonconventional-secretory-pathway
#14
Camilla Stampe Jensen, Shoji Watanabe, Jeroen Ingrid Stas, Jessica Klaphaak, Ayaka Yamane, Nicole Schmitt, Søren-Peter Olesen, James S Trimmer, Hanne Borger Rasmussen, Hiroaki Misonou
Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely expressed in neurons of the CNS. Kv2.1 localizes in high-density cell-surface clusters in the soma and proximal dendrites as well as in the axon initial segment (AIS). Given the crucial roles of both of these compartments in integrating signal input and then generating output, this localization of Kv2.1 is ideal for regulating the overall excitability of neurons. Here we used fluorescence recovery after photobleaching imaging, mutagenesis, and pharmacological interventions to investigate the molecular mechanisms that control the localization of Kv2...
November 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28938641/potential-independent-action-of-sigma-receptor-ligands-through-inhibition-of-the-kv2-1-channel
#15
Xinying Liu, Yingmei Fu, Huan Yang, Timur Mavlyutov, Jun Li, Christopher R McCurdy, Lian-Wang Guo, Bikash R Pattnaik
The sigma-1 receptor (σ1-R) and sigma-2 receptor (σ2-R) are potential drug targets for treatment of cancer, pain, depression, retinal degeneration and other neuronal diseases. Previous reports show that sigma-1 receptor modulates the activities of multiple channels. We are interested in possible sigma receptor modulation of Kv2.1, a K(+) channel abundant in retinal photoreceptors. We tested the effect of established sigma receptor ligands on Kv2.1 channels which were stably expressed in HEK293 cells. Surprisingly, σ1-R antagonists inhibited Kv2...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28867730/up-regulation-of-the-voltage-gated-kv2-1-k-channel-in-the-renal-arterial-myocytes-of-dahl-salt-sensitive-hypertensive-rats
#16
Kazunobu Ogiwara, Susumu Ohya, Yoshiaki Suzuki, Hisao Yamamura, Yuji Imaizumi
Salt-sensitive hypertension induces renal injury via decreased blood flow in the renal artery (RA), and ion channel dysfunction in RA myocytes (RAMs) may be involved in the higher renal vascular resistance. We examined the effects of several voltage-gated K(+) (KV) channel blockers on the resting tension in endothelium-denuded RA strips and delayed-rectifier K(+) currents in RAMs of Dahl salt-sensitive hypertensive rats (Dahl-S) fed with low- (Dahl-LS) and high-salt diets (Dahl-HS). The tetraethylammonium (TEA)-induced contraction in RA strips were significantly larger in Dahl-HS than Dahl-LS...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28861159/relationship-and-mechanism-of-kv2-1-expression-to-adh-secretion-in-rats-with-heart-failure
#17
Jiaxiang Li, Baiyun Tang, Wenbo Zhang, Cuiping Wang, Song Yang, Bao Zhang, Xiuren Gao
OBJECTIVE: To explore the mechanisms of Kv2.1 on the secretion of ADH in rats with heart failure. METHODS: In the animal study, 70 healthy male SD rats were selected. Ligation of coronary heart failure model surgery was performed in 60 rats and sham surgery was performed in the other 10 rats. Q-PCR was used to detect the mRNA expression of Kv2.1 in hypothalamus and heart. The protein expression of Kv2.1 and ADH was detected by western blot. In the cell culture study, hypothalamic neurons were cultured and divided into 7 groups...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28856240/heterogeneity-in-kv2-channel-expression-shapes-action-potential-characteristics-and-firing-patterns-in-ca1-versus-ca2-hippocampal-pyramidal-neurons
#18
Stephanie Palacio, Vivien Chevaleyre, David H Brann, Karl D Murray, Rebecca A Piskorowski, James S Trimmer
The CA1 region of the hippocampus plays a critical role in spatial and contextual memory, and has well-established circuitry, function and plasticity. In contrast, the properties of the flanking CA2 pyramidal neurons (PNs), important for social memory, and lacking CA1-like plasticity, remain relatively understudied. In particular, little is known regarding the expression of voltage-gated K(+) (Kv) channels and the contribution of these channels to the distinct properties of intrinsic excitability, action potential (AP) waveform, firing patterns and neurotransmission between CA1 and CA2 PNs...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28768770/nmda-receptors-mediate-leptin-signaling-and-regulate-potassium-channel-trafficking-in-pancreatic-%C3%AE-cells
#19
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...
September 15, 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
#20
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
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