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https://www.readbyqxmd.com/read/27903742/p2y6-receptor-antagonist-mrs2578-inhibits-neutrophil-activation-and-aggregated-neutrophil-extracellular-trap-formation-induced-by-gout-associated-monosodium-urate-crystals
#1
Payel Sil, Craig P Hayes, Barbara J Reaves, Patrick Breen, Shannon Quinn, Jeremy Sokolove, Balázs Rada
Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27874831/chronic-social-isolation-reduces-5-ht-neuronal-activity-via-upregulated-sk3-calcium-activated-potassium-channels
#2
Derya Sargin, David K Oliver, Evelyn K Lambe
The activity of serotonin (5-HT) neurons is critical for mood regulation. In a mouse model of chronic social isolation, a known risk factor for depressive illness, we show that 5-HT neurons in the dorsal raphe nucleus are less responsive to stimulation. Probing the responsible cellular mechanisms pinpoints a disturbance in the expression and function of small-conductance Ca(2+)-activated K(+) (SK) channels and reveals an important role for both SK2 and SK3 channels in normal regulation of 5-HT neuronal excitability...
November 22, 2016: ELife
https://www.readbyqxmd.com/read/27861914/a-unifying-hypothesis-for-m1-muscarinic-receptor-signalling-in-pyramidal-neurons
#3
Sameera Dasari, Corey Hill, Allan T Gulledge
Gq -coupled muscarinic acetylcholine (ACh) receptors (mAChRs) mediate two distinct electrophysiological responses in cortical pyramidal neurons: transient inhibition driven by calcium-dependent small conductance potassium ("SK") channels, and longer-lasting and voltage-dependent excitation involving non-specific cation channels. Here we examine the interaction of these two cholinergic responses with respect to their contributions to intracellular calcium dynamics, testing the unifying hypothesis that rundown of inhibitory SK responses at resting membrane potentials (RMPs) reflects depletion of intracellular calcium stores, while mAChR-driven excitation acts to refill those stores by promoting voltage-dependent entry of extracellular calcium...
November 12, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27856251/local-calcium-signalling-is-mediated-by-mechanosensitive-ion-channels-in-mesenchymal-stem-cells
#4
Vladislav I Chubinskiy-Nadezhdin, Valeria Y Vasileva, Natalia A Pugovkina, Irina O Vassilieva, Elena A Morachevskaya, Nikolay N Nikolsky, Yuri A Negulyaev
Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs)...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27844406/partial-bladder-outlet-obstruction-is-associated-with-decreased-expression-and-function-of-the-small-conductance-ca-2-activated-k-channel-in-guinea-pig-detrusor-smooth-muscle
#5
Ning Li, Xiaoning He, Zizheng Li, Yili Liu, Ping Wang
PURPOSE: Partial bladder outlet obstruction (PBOO) usually induces overactive bladder (OAB) associated with detrusor overactivity (DO) which is related to the increased contractility of detrusor smooth muscle (DSM). The pharmacological activation of small-conductance Ca(2+)-activated K(+) (SK) channels dramatically attenuates DSM contractility. However, the role of SK channels in the PBOO DSM is less clear. Here, we tested the hypothesis that PBOO is associated with decreased expression and function of SK channels in DSM and that the activation of SK channels is a potential target to regulate DO...
November 14, 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27825825/changes-in-sk-channel-expression-in-the-basal-ganglia-after-partial-nigrostriatal-dopamine-lesions-in-rats-functional-consequences
#6
Christiane Mourre, Christine Manrique, Jeremy Camon, Sabrine Aidi-Knani, Thierry Deltheil, Nathalie Turle-Lorenzo, Gaelle Guiraudie-Capraz, Marianne Amalric
Parkinson's disease (PD) is a progressive neurodegenerative disease originating from the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNC). The small-conductance calcium-activated potassium (SK) channels play an essential role in the regulation of midbrain DA neuron activity patterns, as well as excitability of other types of neurons of the basal ganglia. We therefore questioned whether the SK channel expression in the basal ganglia is modified in parkinsonian rats and how this could impact behavioral performance in a reaction time task...
November 5, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27798131/cocaine-exposure-enhances-the-activity-of-ventral-tegmental-area-dopamine-neurons-via-calcium-impermeable-nmdars
#7
Meaghan Creed, Jennifer Kaufling, Giulia R Fois, Marion Jalabert, Tifei Yuan, Christian Lüscher, Francois Georges, Camilla Bellone
: Potentiation of excitatory inputs onto dopamine neurons of the ventral tegmental area (VTA) induced by cocaine exposure allows remodeling of the mesocorticolimbic circuitry, which ultimately drives drug-adaptive behavior. This potentiation is mediated by changes in NMDAR and AMPAR subunit composition. It remains unknown how this synaptic plasticity affects the activity of dopamine neurons. Here, using rodents, we demonstrate that a single cocaine injection increases the firing rate and bursting activity of VTA dopamine neurons, and that these increases persist for 7 d...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27779751/distinct-subcellular-mechanisms-for-the-enhancement-of-the-surface-membrane-expression-of-sk2-channel-by-its-interacting-proteins-%C3%AE-actinin2-and-filamin-a
#8
Zheng Zhang, Hannah A Ledford, Seojin Park, Wenying Wang, Sassan Rafizadeh, Hyo Jeong Kim, Wilson Xu, Ling Lu, Victor C Lau, Anne A Knowlton, Xiao-Dong Zhang, Ebenezer N Yamoah, Nipavan Chiamvimonvat
The normal function of ion channels depends critically on the precise subcellular localization and the number of channel proteins on the cell surface membrane. Small-conductance, Ca(2+) -activated K(+) channels (SK, KCa 2) are expressed in human atrial myocytes and responsible for shaping atrial action potentials. Understanding the mechanisms of SK channel trafficking may provide new insights into the regulation controlling the repolarization of atrial myocytes. We have previously demonstrated that the C and N termini of SK2 channels interact with actin-binding proteins, α-actinin2 and filamin A, respectively...
October 25, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27742566/atrial-fibrillation-therapeutic-potential-of-atrial-k-channel-blockers
#9
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/27722784/antiarrhythmic-effect-of-the-ca-2-activated-k-sk-channel-inhibitor-ica-combined-with-either-amiodarone-or-dofetilide-in-an-isolated-heart-model-of-atrial-fibrillation
#10
Jeppe Egedal Kirchhoff, Jonas Goldin Diness, Lea Abildgaard, Majid Sheykhzade, Morten Grunnet, Thomas Jespersen
Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide has dose-related ventricular side effects, amiodarone primarily has adverse non-cardiac effects. Pharmacological inhibition of small conductance Ca(2+)-activated K(+) (SK) channels has recently been reported to be antiarrhythmic in a number of animal AF models. In a Langendorff model of acutely induced AF on guinea pig hearts, it was investigated whether a combination of the SK channel blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) together with either dofetilide or amiodarone provided a synergistic effect...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27698359/observation-of-a-hybrid-state-of-tamm-plasmons-and-microcavity-exciton-polaritons
#11
Sk Shaid-Ur Rahman, Thorsten Klein, Sebastian Klembt, Jürgen Gutowski, Detlef Hommel, Kathrin Sebald
We present evidence for the existence of a hybrid state of Tamm plasmons and microcavity exciton polaritons in a II-VI material based microcavity sample covered with an Ag metal layer. The bare cavity mode shows a characteristic anticrossing with the Tamm-plasmon mode, when microreflectivity measurements are performed for different detunings between the Tamm plasmon and the cavity mode. When the Tamm-plasmon mode is in resonance with the cavity polariton four hybrid eigenstates are observed due to the coupling of the cavity-photon mode, the Tamm-plasmon mode, and the heavy- and light-hole excitons...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27683906/hypocretin-orexin-peptides-alter-spike-encoding-by-serotonergic-dorsal-raphe-neurons-through-two-distinct-mechanisms-that-increase-the-late-afterhyperpolarization
#12
Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N Ross, Christopher S Leonard
UNLABELLED: Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), but was not blocked by UCL2077, an antagonist of sAHPs in some neurons...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27646472/activation-of-atp-sensitive-potassium-channels-enhances-dmt1-mediated-iron-uptake-in-sk-n-sh-cells-in-vitro
#13
Xixun Du, Huamin Xu, Limin Shi, Zhifeng Jiang, Ning Song, Hong Jiang, Junxia Xie
Iron importer divalent metal transporter 1 (DMT1) plays a crucial role in the nigal iron accumulation in Parkinson's disease (PD). Membrane hyperpolarization is one of the factors that could affect its iron transport function. Besides iron, selective activation of the ATP-sensitive potassium (KATP) channels also contributes to the vulnerability of dopaminergic neurons in PD. Interestingly, activation of KATP channels could induce membrane hyperpolarization. Therefore, it is of vital importance to study the effects of activation of KATP channels on DMT1-mediated iron uptake function...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27616575/endothelium-independent-vasorelaxant-effect-of-20-s-protopanaxadiol-on-isolated-rat-thoracic-aorta
#14
Lu Gan, Zhen-Hua Wang, Hong Zhang, Xin Zhou, Hui Zhou, Chao Sun, Jing Si, Rong Zhou, Cheng-Jun Ma, Ji Li
AIM: Ginsenosides are considered to be the major pharmacologically active ginseng constituents, whereas 20(S)-protopanaxadiol [20(S)-PPD] is the active metabolite of ginsenosides in gut. In this study we investigated the effect of 20(S)-PPD on isolated rat thoracic aortas as well as its vasorelaxant mechanisms. METHODS: Aortic rings with or without endothelium were prepared from Wistar rats and suspended in organ-chambers. The changes in tension of the preparations were recorded through isometric transducers connected to a data acquisition system...
December 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27555660/dynamic-dna-methylation-regulates-neuronal-intrinsic-membrane-excitability
#15
Jarrod P Meadows, Mikael C Guzman-Karlsson, Scott Phillips, Jordan A Brown, Sarah K Strange, J David Sweatt, John J Hablitz
Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory-related plasticity also includes alterations in intrinsic membrane excitability mediated by changes in the abundance or activity of ion channels in the plasma membrane, which sets the threshold for action potential generation...
August 23, 2016: Science Signaling
https://www.readbyqxmd.com/read/27455901/effects-of-k-channel-openers-on-spontaneous-action-potentials-in-detrusor-smooth-muscle-of-the-guinea-pig-urinary-bladder
#16
Hiroaki Takagi, Hikaru Hashitani
The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM)...
October 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27442679/kcnn2-polymorphisms-and-cardiac-tachyarrhythmias
#17
Chih-Chieh Yu, Tsai Chia-Ti, Pei-Lung Chen, Cho-Kai Wu, Fu-Chun Chiu, Fu-Tien Chiang, Peng-Sheng Chen, Chi-Ling Chen, Lian-Yu Lin, Jyh-Ming Juang, Li-Ting Ho, Ling-Ping Lai, Wei-Shiung Yang, Jiunn-Lee Lin
Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans...
July 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27432863/small-conductance-ca2-activated-potassium-channels-negatively-regulate-aldosterone-secretion-in-human-adrenocortical-cells
#18
Tingting Yang, Hai-Liang Zhang, Qingnan Liang, Yingtang Shi, Yan-Ai Mei, Paula Q Barrett, Changlong Hu
Aldosterone, which plays a key role in maintaining water and electrolyte balance, is produced by zona glomerulosa cells of the adrenal cortex. Autonomous overproduction of aldosterone from zona glomerulosa cells causes primary hyperaldosteronism. Recent clinical studies have highlighted the pathological role of the KCNJ5 potassium channel in primary hyperaldosteronism. Our objective was to determine whether small-conductance Ca(2+)-activated potassium (SK) channels may also regulate aldosterone secretion in human adrenocortical cells...
September 2016: Hypertension
https://www.readbyqxmd.com/read/27379631/enteric-inhibitory-neurotransmission-starting-down-under
#19
Kenton M Sanders
The idea of an inhibitory innervation in the gut came from Geoff Burnstock's group at the University of Melbourne in the 1960s. Being resistant to antagonists of norepinephrine and acetylcholine, enteric inhibitory neurotransmission became known as non-cholinergic, non-adrenergic (NANC) neurotransmission. ATP (or a closely related nucleotide) was proposed as the inhibitory neurotransmitter based on release of purines during nerve stimulation and similarities between responses to ATP and transmural nerve stimulation in several gut preparations...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27377724/effect-of-knockout-of-%C3%AE-2%C3%AE-1-on-action-potentials-in-mouse-sensory-neurons
#20
Wojciech Margas, Laurent Ferron, Manuela Nieto-Rostro, Arnold Schwartz, Annette C Dolphin
Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency...
August 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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