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https://www.readbyqxmd.com/read/28087137/nos-interacting-protein-nosip-is-increased-in-the-colon-of-patients-with-hirschsprung-s-disease
#1
Anne-Marie O'Donnell, David Coyle, Prem Puri
PURPOSE: Voltage-dependent K(+) channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.1-Kv7.5. A recent study identified the potassium channel Kv7.5 as having a role in the excitability of ICC-IM in the mouse colon...
January 3, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28054303/amino-acid-properties-of-trafficking-determinants-in-the-outer-pore-forming-region-of-kv1-potassium-channels-in-cell-lines
#2
Barbara Gomez, Jing Zhu, Esperanza Recio-Pinto, William B Thornhill
Different classes of Kv1 potassium channels have different trafficking patterns despite having very similar amino acid sequences. Two amino acids responsible for these differences have been identified in the outer pore turret region of Kv1.1 and Kv1.4. Here we tested a series of substitutions at these two determinants on Kv1.4. All P506 substitutions tested resulted in a significant decrease in surface protein, total protein, and protein half-life, indicating that proline is required at 506 to stabilize protein conformation and increase trafficking to the cell surface...
January 5, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28011270/h2s-inhibits-angiotensin-ii-induced-atrial-kv1-5-upregulation-by-attenuating-nox4-mediated-ros-generation-during-atrial-fibrillation
#3
Guihua Lu, Chenggui Xu, Kaiyu Tang, Juhong Zhang, Qinglang Li, Longyun Peng, Yesong Wang, Zhibin Huang, Xiuren Gao
Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study...
December 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27958660/angiotensin-ii-reduces-the-surface-abundance-of-kv1-5-channels-in-arterial-myocytes-to-stimulate-vasoconstriction
#4
Michael W Kidd, Simon Bulley, Jonathan H Jaggar
Smooth muscle cells (myocytes) of resistance-size arteries express several different voltage-dependent K(+) (KV ) channels, including KV 1.5 and KV 2.1, which regulate contractility. Myocyte KV currents are inhibited by vasoconstrictors, including angiotensin II (Ang II), but mechanisms involved are unclear. Here, we tested the hypothesis that Ang II inhibits KV currents by reducing the plasma membrane abundance of KV channels in myocytes. Ang II (2 h) reduced surface and total KV 1.5 protein in rat mesenteric arteries...
December 13, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27916464/subtype-specific-block-of-voltage-gated-k-channels-by-%C3%AE-conopeptides
#5
Enrico Leipold, Florian Ullrich, Markus Thiele, Alesia A Tietze, Heinrich Terlau, Diana Imhof, Stefan H Heinemann
The neurotoxic cone snail peptide μ-GIIIA specifically blocks skeletal muscle voltage-gated sodium (NaV1.4) channels. The related conopeptides μ-PIIIA and μ-SIIIA, however, exhibit a wider activity spectrum by also inhibiting the neuronal NaV channels NaV1.2 and NaV1.7. Here we demonstrate that those μ-conopeptides with a broader target range also antagonize select subtypes of voltage-gated potassium channels of the KV1 family: μ-PIIIA and μ-SIIIA inhibited KV1.1 and KV1.6 channels in the nanomolar range, while being inactive on subtypes KV1...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#6
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27872215/intramolecular-interactions-that-control-voltage-sensitivity-in-the-jshak1-potassium-channel-from-polyorchis-penicillatus
#7
Nazlee Sharmin, Warren J Gallin
Voltage-gated potassium ion (Kv) channel proteins respond to changes in membrane potential by changing the probability of K(+) flux through an ion-selective pore. Kv channels from different paralogous and orthologous families have widely varying V50 values. The voltage-sensing transmembrane helices (S4) of different channels contain 4-7 basic residues that are responsible for transducing changes in transmembrane potential into the energy required to shift the equilibrium between the open- and closed-channel conformations...
November 21, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27872049/contribution-of-kv1-5-channel-to-h2o2-induced-human-arteriolar-dilation-and-its-modulation-by-coronary-artery-disease
#8
Yoshinori Nishijima, Sheng Cao, Dawid S Chabowski, Ankush Korishettar, Alyce Ge, Xiaodong Zheng, Rodney Sparapani, David D Gutterman, David X Zhang
RATIONALE: Hydrogen peroxide (H2O2) regulates vascular tone in the human microcirculation under physiological and pathophysiological conditions. It dilates arterioles by activating BKCa channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) as compared to those with CAD remain unknown. OBJECTIVE: We hypothesize that H2O2-elicited dilation involves different K(+) channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation during disease...
November 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27816768/human-immunodeficiency-virus-protein-tat-induces-oligodendrocyte-injury-by-enhancing-outward-k-current-conducted-by-kv1-3
#9
Han Liu, Jianuo Liu, Enquan Xu, Guihua Tu, Minglei Guo, Shangdong Liang, Huangui Xiong
Brain white matter damage is frequently detected in patients infected with human immunodeficiency virus type 1 (HIV-1). White matter is composed of neuronal axons sheathed by oligodendrocytes (Ols), the myelin-forming cells in central nervous system. Ols are susceptible to HIV-1 viral trans-activator of transcription (Tat) and injury of Ols results in myelin sheath damage. It has been demonstrated that activation of voltage-gated K(+) (KV) channels induces cell apoptosis and Ols predominantly express K(+) channel KV1...
January 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27765883/inhibitory-effects-of-telmisartan-on-culture-and-proliferation-of-and-kv1-3-potassium-channel-expression-in-peripheral-blood-cd4-t-lymphocytes-from-xinjiang-kazakh-patients-with-hypertension
#10
Sha-Sha Huang, Qiu-Bing Zhang, Qing-Yan Yuan, Si-Li He, Yuan-Ming Zhang
INTRODUCTION: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4(+) T lymphocytes derived from Xinjiang Kazakh patients with hypertension. METHODS: CD4(+) T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27760355/extracellular-linkers-completely-transplant-the-voltage-dependence-from-kv1-2-ion-channels-to-kv2-1
#11
Fredrik Elinder, Michael Madeja, Hugo Zeberg, Peter Århem
The transmembrane voltage needed to open different voltage-gated K (Kv) channels differs by up to 50 mV from each other. In this study we test the hypothesis that the channels' voltage dependences to a large extent are set by charged amino-acid residues of the extracellular linkers of the Kv channels, which electrostatically affect the charged amino-acid residues of the voltage sensor S4. Extracellular cations shift the conductance-versus-voltage curve, G(V), by interfering with these extracellular charges...
October 18, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27742566/atrial-fibrillation-therapeutic-potential-of-atrial-k-channel-blockers
#12
REVIEW
Ursula Ravens, Katja E Odening
Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K(+)) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets...
October 12, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27731805/effects-of-ginseng-spikenard-heart-nourishing-capsule-on-inactivation-of-c-type-kv1-4-potassium-channel
#13
Zhi-Quan Wang, Xue-Jun Jiang, Guang-Yu Zhang, Ming Chen, Chuan-Feng Tong, Dong Zhang
This research is to explore the effects of traditional Chinese medicine Ginseng-spikenard heart-nourishing capsule on the inactivation of c-type Kv1.4 channels (Kv1.4∆N) in Xenopus laevis oocytes with two-electrode voltageclamp technique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4δN channels. During recording, oocytes were continuously perfused with ND96 solution (control group) and solution prepared from Ginseng-spikenard heart-nourishing capsule (experimental group)...
September 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27696527/differential-kv1-3-kca3-1-and-kir2-1-expression-in-classically-and-alternatively-activated-microglia
#14
Hai M Nguyen, Eva M Grössinger, Makoto Horiuchi, Kyle W Davis, Lee-Way Jin, Izumi Maezawa, Heike Wulff
Microglia are highly plastic cells that can assume different phenotypes in response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) promote differentiation into classically activated M1-like microglia, which produce high levels of pro-inflammatory cytokines and nitric oxide and are thought to contribute to neurological damage in ischemic stroke and Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti-inflammatory effects and tissue repair. We here investigated whether these microglia subsets vary in their K(+) channel expression by differentiating neonatal mouse microglia into M(LPS) and M(IL-4) microglia and studying their K(+) channel expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry...
January 2017: Glia
https://www.readbyqxmd.com/read/27638047/comparison-of-voltage-gated-k-currents-in-arterial-myocytes-with-heterologously-expressed-k-v-subunits
#15
Robert H Cox, Samantha Fromme
We have shown that three components contribute to functional voltage gated K(+) (K v) currents in rat small mesenteric artery myocytes: (1) Kv1.2 plus Kv1.5 with Kvβ1.2 subunits, (2) Kv2.1 probably associated with Kv9.3 subunits, and (3) Kv7.4 subunits. To confirm and address subunit stoichiometry of the first two, we have compared the biophysical properties of K v currents in small mesenteric artery myocytes with those of Kv subunits heterologously expressed in HEK293 cells using whole cell voltage clamp methods...
December 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27582084/kcna4-deficiency-leads-to-a-syndrome-of-abnormal-striatum-congenital-cataract-and-intellectual-disability
#16
Namik Kaya, Maysoon Alsagob, Maria Cristina D'Adamo, Albandary Al-Bakheet, Sonia Hasan, Maria Muccioli, Faten B Almutairi, Rawan Almass, Mazhor Aldosary, Dorota Monies, Osama M Mustafa, Banan Alyounes, Rosan Kenana, Jawaher Al-Zahrani, Eva Naim, Faisal S Binhumaid, Alya Qari, Fatema Almutairi, Brian Meyer, Timothy F Plageman, Mauro Pessia, Dilek Colak, Mohammed Al-Owain
BACKGROUND: Voltage-gated potassium channels are highly diverse proteins representing the most complex class of voltage-gated ion channels from structural and functional perspectives. Deficiency of these channels usually results in various human disorders. OBJECTIVES: To describe a novel autosomal recessive syndrome associated with KCNA4 deficiency leading to congenital cataract, abnormal striatum, intellectual disability and attention deficit hyperactivity disorder...
August 31, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27527983/regulation-of-brain-ppargamma2-contributes-to-ketogenic-diet-anti-seizure-efficacy
#17
Timothy A Simeone, Stephanie A Matthews, Kaeli K Samson, Kristina A Simeone
The ketogenic diet (KD) is an effective therapy primarily used in pediatric patients whom are refractory to current anti-seizure medications. The mechanism of the KD is not completely understood, but is thought to involve anti-inflammatory and anti-oxidant processes. The nutritionally-regulated transcription factor peroxisome proliferator activated receptor gamma, PPARγ, regulates genes involved in anti-inflammatory and anti-oxidant pathways. Moreover, endogenous ligands of PPARγ include fatty acids suggesting a potential role in the effects of the KD...
January 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27379187/kv1-and-kv3-potassium-channels-identified-at-presynaptic-terminals-of-the-corticostriatal-synapses-in-rat
#18
David Meneses, Ana V Vega, Francisco Miguel Torres-Cruz, Jaime Barral
In the last years it has been increasingly clear that KV-channel activity modulates neurotransmitter release. The subcellular localization and composition of potassium channels are crucial to understanding its influence on neurotransmitter release. To investigate the role of KV in corticostriatal synapses modulation, we combined extracellular recording of population-spike and pharmacological blockage with specific and nonspecific blockers to identify several families of KV channels. We induced paired-pulse facilitation (PPF) and studied the changes in paired-pulse ratio (PPR) before and after the addition of specific KV blockers to determine whether particular KV subtypes were located pre- or postsynaptically...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27317303/the-effects-of-telmisartan-on-the-nuclear-factor-of-activated-t-lymphocytes-signalling-pathway-in-hypertensive-patients
#19
Sha-Sha Huang, Si-Li He, Yuan-Ming Zhang
HYPOTHESIS: Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China...
April 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27281482/polyunsaturated-fatty-acids-inhibit-kv1-4-by-interacting-with-positively-charged-extracellular-pore-residues
#20
N E Farag, D Jeong, T Claydon, J Warwicker, M R Boyett
Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K(+) channel inactivation by an unknown site and mechanism. The effects of ω-6 and ω-3 PUFAs were investigated on the heterologously expressed Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation (Kd, 15-43 μM). C-type inactivation was affected by extracellular H(+) and K(+) as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abolished on raising K(+) Replacement of two positively charged residues in the extracellular pore (H508 and K532) abolished the effects of the PUFAs (and extracellular H(+) and K(+)) on C-type inactivation but had no effect on the lipoelectric modulation of voltage sensor activation, suggesting two separable interaction sites/mechanisms of action of PUFAs...
August 1, 2016: American Journal of Physiology. Cell Physiology
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