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https://www.readbyqxmd.com/read/28417339/expression-and-function-of-the-small-conductance-ca-2-activated-k-channel-is-decreased-in-urinary-bladder-smooth-muscle-cells-from-female-guinea-pig-with-partial-bladder-outlet-obstruction
#1
Ning Li, Honglin Ding, Xiaoning He, Zizheng Li, Yili Liu
PURPOSE: Overactive bladder (OAB), usually accompanied by partial bladder outlet obstruction (PBOO), is associated with detrusor overactivity (DO) which is related to the increased urinary bladder smooth muscle (UBSM) cells excitability. Small-conductance Ca(2+)-activated K(+) (SK) channels play a constitutive regulatory role of UBSM excitability and contractility. PBOO is associated with the decreased SK channels mRNA expression and the attenuated regulative effect of SK channels on UBSM contractility...
April 17, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28356481/sk-channel-inhibition-mediates-the-initiation-and-amplitude-modulation-of-synchronized-burst-firing-in-the-spinal-cord
#2
Amr A Mahrous, Sherif M Elbasiouny
Burst firing in motoneurons represents the basis for generating meaningful movements. Neuromodulators and inhibitory receptor blockers cocktails have been used for years to induce burst firing in vitro; however, the ionic mechanisms in the motoneuron membrane which contribute to burst initiation and amplitude modulation are not fully understood. Small conductance Ca2+-activated potassium channels (SK channels) regulate excitatory inputs and firing output of motoneurons and interneurons and, therefore, are a candidate for mediating bursting behavior...
March 29, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28346695/contribution-of-small-conductance-k-channels-to-sinoatrial-node-pacemaker-activity-insights-from-atrial-specific-na-ca-2-exchange-knockout-mice
#3
Angelo G Torrente, Rui Zhang, Heidi Wang, Audrey Zaini, Brian Kim, Xin Yue, Kenneth D Philipson, Joshua I Goldhaber
Small conductance K(+) (SK) channels have been implicated as modulators of spontaneous depolarization and electrical conduction that may be involved in cardiac arrhythmia. However, neither their presence nor their contribution to sinoatrial node (SAN) pacemaker activity have been investigated. Using quantitative PCR (q-PCR), immunostaining and patch clamp recordings of membrane current and voltage, we identified all three SK isoforms (SK1, SK2 and SK3) in mouse SAN. Inhibition of SK channels with the specific blocker apamin prolonged action potentials (APs) in isolated SAN cells...
March 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28331181/multi-walled-carbon-nanotubes-act-as-a-chemokine-and-recruit-macrophages-by-activating-the-plc-ip3-crac-channel-signaling-pathway
#4
Hui Li, Xiao-Qiu Tan, Li Yan, Bo Zeng, Jie Meng, Hai-Yan Xu, Ji-Min Cao
The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322838/effect-of-antiarrhythmic-drugs-on-small-conductance-calcium-activated-potassium-channels
#5
Rafel Simó-Vicens, Daniel R P Sauter, Morten Grunnet, Jonas G Diness, Bo H Bentzen
Atrial fibrillation (AF) is the most common type of arrhythmia. Current pharmacological treatment for AF is moderately effective and/or increases the risk of serious ventricular adverse effects. To avoid ventricular adverse effects, a new target has been considered, the small conductance calcium-activated K(+) channels (KCa2.X, SK channels). In the heart, KCa2.X channels are functionally more important in atria compared to ventricles, and pharmacological inhibition of the channel confers atrial selective prolongation of the cardiac action potential and converts AF to sinus rhythm in animal models of AF...
May 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#6
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/28294142/inosine-attenuates-spontaneous-activity-in-the-rat-neurogenic-bladder-through-an-a2b-pathway
#7
Claire Doyle, Vivian Cristofaro, Bryan S Sack, Stefan N Lukianov, Mattias Schäfer, Yeun Goo Chung, Maryrose P Sullivan, Rosalyn M Adam
Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28285409/pharmacological-blockade-of-small-conductance-ca-2-activated-k-channels-by-ica-reduces-arrhythmic-load-in-rats-with-acute-myocardial-infarction
#8
Laura A Hundahl, Stefan M Sattler, Lasse Skibsbye, Jonas G Diness, Jacob Tfelt-Hansen, Thomas Jespersen
Acute myocardial infarction (AMI) with development of ventricular fibrillation (VF) is a common cause of sudden cardiac death (SCD). At present, no pharmacological treatment has successfully been able to prevent VF in the acute stage of AMI. This study investigates the antiarrhythmic effect of inhibiting small conductance Ca(2+)-activated K(+) (SK) channels using the pore blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) in AMI rats. Acute coronary ligation was performed in 26 anesthetized rats, and ECG, monophasic action potentials (MAPs), and ventricular effective refractory period (vERP) were recorded...
March 11, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28282037/sk2-channels-regulate-mitochondrial-respiration-and-mitochondrial-ca-2-uptake
#9
Birgit Honrath, Lina Matschke, Tammo Meyer, Lena Magerhans, Fabiana Perocchi, Goutham K Ganjam, Hans Zischka, Cornelius Krasel, Albert Gerding, Barbara M Bakker, Moritz Bünemann, Stefan Strack, Niels Decher, Carsten Culmsee, Amalia M Dolga
Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca(2+)]m uptake upon SK channel activation as detected by time lapse mitochondrial Ca(2+) measurements with the Ca(2+)-binding mitochondria-targeted aequorin and FRET-based [Ca(2+)]m probes...
March 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28280420/chronic-ca-2-influx-through-voltage-dependent-ca-2-channels-enhance-delayed-rectifier-k-currents-via-activating-src-family-tyrosine-kinase-in-rat-hippocampal-neurons
#10
Yoon-Sil Yang, Sang-Chan Jeon, Dong-Kwan Kim, Su-Yong Eun, Sung-Cherl Jung
Excessive influx and the subsequent rapid cytosolic elevation of Ca(2+) in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca(2+) level in normal as well as pathological conditions. Delayed rectifier K(+) channels (IDR channels) play a role to suppress membrane excitability by inducing K(+) outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca(2+)-mediated excitotoxic conditions...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28277938/sk-channel-subtypes-enable-parallel-optimized-coding-of-behaviorally-relevant-stimulus-attributes-a-review
#11
Chengjie G Huang, Maurice J Chacron
Ion channels play essential roles toward determining how neurons respond to sensory input to mediate perception and behavior. Small conductance calcium-activated potassium (SK) channels are found ubiquitously throughout the brain and have been extensively characterized both molecularly and physiologically in terms of structure and function. It is clear that SK channels are key determinants of neural excitability as they mediate important neuronal response properties such as spike frequency adaptation. However, the functional roles of the different known SK channel subtypes are not well understood...
March 1, 2017: Channels
https://www.readbyqxmd.com/read/28262027/bis-15-crown-5-ether-pillar-5-arene-k-responsive-channels
#12
Wei-Xu Feng, Zhanhu Sun, Yan Zhang, Yves-Marie Legrand, Eddy Petit, Cheng-Yong Su, Mihail Barboiu
An artificial selective K(+) channel is formed from the supramolecular organization on bis(benzo-15-crown-5- ether-ureido)-pillar[5]arene compound. This channel achieves a selectivity of SK(+)/Na(+) = 5 for an initial transport rate of kK(+) = 3.2 × 10(-3) s(-1). The cation-file diffusion occurs via selective macrocyclic-filters anchored on inactive supporting pillar[5]arene relays. The sandwich-type binding geometry of the K(+) cation by two 15-crown-5 moieties sites is a key feature influencing channel efficiency...
March 6, 2017: Organic Letters
https://www.readbyqxmd.com/read/28208379/prediction-of-the-moments-in-advection-diffusion-lattice-boltzmann-method-i-truncation-dispersion-skewness-and-kurtosis
#13
Irina Ginzburg
The effect of the heterogeneity in the soil structure or the nonuniformity of the velocity field on the modeled resident time distribution (RTD) and breakthrough curves is quantified by their moments. While the first moment provides the effective velocity, the second moment is related to the longitudinal dispersion coefficient (k_{T}) in the developed Taylor regime; the third and fourth moments are characterized by their normalized values skewness (Sk) and kurtosis (Ku), respectively. The purpose of this investigation is to examine the role of the truncation corrections of the numerical scheme in k_{T}, Sk, and Ku because of their interference with the second moment, in the form of the numerical dispersion, and in the higher-order moments, by their definition...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28162597/-355-riluzole-actions-on-sk-channels-in-the-amygdala-in-acute-arthritic-and-chronic-neuropathic-pain
#14
J Thompson, G Ji, V Neugebauer
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28115487/cholinergic-interneurons-underlie-spontaneous-dopamine-release-in-nucleus-accumbens
#15
Jordan T Yorgason, Douglas M Zeppenfeld, John T Williams
The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine...
February 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28108814/the-small-neurotoxin-apamin-blocks-not-only-small-conductance-ca-2-activated-k-channels-sk-type-but-also-the-voltage-dependent-kv1-3-channel
#16
Patrick Voos, Mehtap Yazar, René Lautenschläger, Oliver Rauh, Anna Moroni, Gerhard Thiel
Apamin is frequently used as a specific blocker of small-conductance Ca(2+)-activated (SK type) K(+) channels. Here we show that the small neurotoxin is not as specific as anticipated. It is also a high-affinity inhibitor with an IC50 of 13 nM of the Kv1.3 channel; it blocks the latter with potency similar to the Kv1.3 blocker PAP-1. Since SK type channels and Kv1.3 channels are frequently coexpressed in different tissues such as cells of the immune system, apamin must be used with caution as a pharmacological tool...
January 20, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28096168/sk-channel-enhancers-attenuate-ca2-dependent-arrhythmia-in-hypertrophic-hearts-by-regulating-mito-ros-dependent-oxidation-and-activity-of-ryr
#17
Tae Yun Kim, Radmila Terentyeva, Karim H F Roder, Weiyan Li, Man Liu, Ian Greener, Shanna Hamilton, Iuliia Polina, Kevin R Murphy, Richard T Clements, Samuel C Dudley, Gideon Koren, Bum-Rak Choi, Dmitry Terentyev
Aims: Plasmamembrane small conductance Ca2+-activated K+ (SK) channels were implicated in ventricular arrhythmias in infarcted and failing hearts. Recently, SK channels were detected in the inner mitochondria membrane (IMM) (mSK), and their activation protected from acute ischaemia-reperfusion injury by reducing intracellular levels of reactive oxygen species (ROS). We hypothesized that mSK play an important role in regulating mitochondrial function in chronic cardiac diseases. We investigated the role of mSK channels in Ca2+-dependent ventricular arrhythmia using rat model of cardiac hypertrophy induced by banding of the ascending aorta thoracic aortic banding (TAB)...
March 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28093473/differential-regulation-of-nmda-receptor-mediated-transmission-by-sk-channels-underlies-dorsal-ventral-differences-in-dynamics-of-schaffer-collateral-synaptic-function
#18
Walter E Babiec, Shekib A Jami, Ryan Guglietta, Patrick B Chen, Thomas J O'Dell
Behavioral, physiological, and anatomical evidence indicates that the dorsal and ventral zones of the hippocampus have distinct roles in cognition. How the unique functions of these zones might depend on differences in synaptic and neuronal function arising from the strikingly different gene expression profiles exhibited by dorsal and ventral CA1 pyramidal cells is unclear. To begin to address this question, we investigated the mechanisms underlying differences in synaptic transmission and plasticity at dorsal and ventral Schaffer collateral (SC) synapses in the mouse hippocampus...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28089668/ebio-does-not-induce-cardiomyogenesis-in-human-pluripotent-stem-cells-but-modulates-cardiac-subtype-enrichment-by-lineage-selective-survival
#19
Monica Jara-Avaca, Henning Kempf, Michael Rückert, Diana Robles-Diaz, Annika Franke, Jeanne de la Roche, Martin Fischer, Daniela Malan, Philipp Sasse, Wladimir Solodenko, Gerald Dräger, Andreas Kirschning, Ulrich Martin, Robert Zweigerdt
Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca(2+)-activated potassium channels (SKs 1-4). Investigating EBIO in human pluripotent stem cells (PSCs), we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency...
February 14, 2017: Stem Cell 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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