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https://www.readbyqxmd.com/read/28738160/atrial-selective-k-channel-blockers-potential-antiarrhythmic-drugs-in-atrial-fibrillation
#1
Ursula Ravens
In the wake of demographic change in Western countries atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. In this lecture, I will address drugs acting on potassium (K+) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles...
July 24, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28714070/a-reduction-in-sk-channels-contributes-to-increased-activity-of-hypothalamic-magnocellular-neurons-during-heart-failure
#2
H C Ferreira-Neto, V Biancardi, J E Stern
Small conductance Ca(2+) -activated K(+) channels (SK) play an important role in regulating MNCs activity and hormone release from the posterior pituitary. Moreover, an enhanced SK activity contributes to MNCs' adaptive responses to a physiological challenge, such as lactation. Still, whether changes in SK function/expression contribute to exacerbated MNCs activity during diseases like heart failure (HF), remains unknown. Here, we used a combination of patch-clamp electrophysiology, confocal Ca(2+) imaging and molecular biology in a rat model of ischemic HF...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28701955/therapeutic-properties-of-bioactive-compounds-from-different-honeybee-products
#3
REVIEW
Laura Cornara, Marco Biagi, Jianbo Xiao, Bruno Burlando
Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28701749/calcium-activated-sk-channels-control-firing-regularity-by-modulating-sodium-channel-availability-in-midbrain-dopamine-neurons
#4
Rajeshwari Iyer, Mark A Ungless, Aldo A Faisal
Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area regulate behaviours such as reward-related learning, and motor control. Dysfunction of these neurons is implicated in Schizophrenia, addiction to drugs, and Parkinson's disease. While some dopamine neurons fire single spikes at regular intervals, others fire irregular single spikes interspersed with bursts. Pharmacological inhibition of calcium-activated potassium (SK) channels increases the variability in their firing pattern, sometimes also increasing the number of spikes fired in bursts, indicating that SK channels play an important role in maintaining dopamine neuron firing regularity and burst firing...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28682239/physiological-and-pathophysiological-control-of-synaptic-glun2b-nmda-receptors-by-the-c-terminal-domain-of-amyloid-precursor-protein
#5
Paula A Pousinha, Xavier Mouska, Elisabeth F Raymond, Carole Gwizdek, Ghien Dhib, Gwenola Poupon-Silvestre, Laure-Emmanuelle Zaragosi, Camilla Giudici, Ingrid Bethus, Emilie Pacary, Michael Willem, Hélène Marie
The amyloid precursor protein (APP) harbors physiological roles at synapses and is central to Alzheimer's disease (AD) pathogenesis. Evidence suggests that APP intracellular domain (AICD) could regulate synapse function, but the underlying molecular mechanisms remain unknown. We addressed AICD actions at synapses, per se, combining in-vivo AICD expression, ex-vivo AICD delivery or APP knock-down by in utero electroporation of shRNAs with whole-cell electrophysiology. We report a critical physiological role of AICD in controlling GluN2B-containing NMDA receptors (NMDARs) at immature excitatory synapses, via a transcription-dependent mechanism...
July 6, 2017: ELife
https://www.readbyqxmd.com/read/28613412/myoendothelial-coupling-through-cx40-contributes-to-edh-induced-vasodilation-in-murine-renal-arteries-evidence-from-experiments-and-modelling
#6
Jens Christian Brasen, Cor de Wit, Charlotte Mehlin Sorensen
Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles but the exact mechanisms are still unknown AIM: to investigate the role of vascular gap junctions and potassium channels in the renal endothelial derived hyperpolarization. METHODS: in interlobar arteries from wild-type and connexin40 knock-out mice we assessed the role of calcium activated small (SK) and intermediate (IK) conductance potassium channels...
June 14, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28596131/control-of-anterior-pituitary-cell-excitability-by-calcium-activated-potassium-channels
#7
REVIEW
Michael J Shipston
In anterior pituitary endocrine cells, large (BK), small (SK) and intermediate (IK) conductance calcium activated potassium channels are key determinants in shaping cellular excitability in a cell type- and context-specific manner. Indeed, these channels are targeted by multiple signaling pathways that stimulate or inhibit cellular excitability. BK channels can, paradoxically, both promote electrical bursting as well as terminate bursting and spiking dependent upon intrinsic BK channel properties and proximity to voltage gated calcium channels in somatotrophs, lactotrophs and corticotrophs...
June 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28591834/cholinergic-grb2-associated-binding-protein-1-regulates-cognitive-function
#8
Nan-Nan Lu, Chao Tan, Ning-He Sun, Ling-Xiao Shao, Xiu-Xiu Liu, Yin-Ping Gao, Rong-Rong Tao, Quan Jiang, Cheng-Kun Wang, Ji-Yun Huang, Kui Zhao, Guang-Fa Wang, Zhi-Rong Liu, Kohji Fukunaga, Ying-Mei Lu, Feng Han
Grb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer's disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons...
June 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28550095/small-conductance-calcium-activated-potassium-current-in-normal-rabbit-cardiac-purkinje-cells
#9
Thomas A Reher, Zhuo Wang, Chia-Hsiang Hsueh, Po-Cheng Chang, Zhenwei Pan, Mohineesh Kumar, Jheel Patel, Jian Tan, Changyu Shen, Zhenhui Chen, Michael C Fishbein, Michael Rubart, Penelope Boyden, Peng-Sheng Chen
BACKGROUND: Purkinje cells (PCs) are important in cardiac arrhythmogenesis. Whether small-conductance calcium-activated potassium (SK) channels are present in PCs remains unclear. We tested the hypotheses that subtype 2 SK (SK2) channel proteins and apamin-sensitive SK currents are abundantly present in PCs. METHODS AND RESULTS: We studied 25 normal rabbit ventricles, including 13 patch-clamp studies, 4 for Western blotting, and 8 for immunohistochemical staining...
May 26, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28511953/small-conductance-ca-2-activated-k-channels-in-the-plasma-membrane-mitochondria-and-the-er-pharmacology-and-implications-in-neuronal-diseases
#10
REVIEW
Birgit Honrath, Inge E Krabbendam, Carsten Culmsee, Amalia M Dolga
Ca(2+)-activated K(+) (KCa) channels regulate after-hyperpolarization in many types of neurons in the central and peripheral nervous system. Small conductance Ca(2+)-activated K(+) (KCa2/SK) channels, a subfamily of KCa channels, are widely expressed in the nervous system, and in the cardiovascular system. Voltage-independent SK channels are activated by alterations in intracellular Ca(2+) ([Ca(2+)]i) which facilitates the opening of these channels through binding of Ca(2+) to calmodulin that is constitutively bound to the SK2 C-terminus...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28502716/neuropeptides-predicted-from-the-transcriptome-analysis-of-the-gray-garden-slug-deroceras-reticulatum
#11
Seung-Joon Ahn, Ruth Martin, Sujaya Rao, Man-Yeon Choi
The gray garden slug, Deroceras reticulatum (Gastropoda: Pulmonata), is one of the most common terrestrial molluscs. Research for this slug has focused mainly on its ecology, biology, and management due to the severe damage it causes on a wide range of vegetables and field crops. However, little is known about neuropeptides and hormonal signalings. This study, therefore, aimed to establish the transcriptome of D. reticulatum and to identify a comprehensive repertoire of neuropeptides in this slug. Illumina high-throughput sequencing of the whole body transcriptome of D...
May 11, 2017: Peptides
https://www.readbyqxmd.com/read/28495974/long-term-depression-of-intrinsic-excitability-accompanied-by-the-synaptic-depression-in-the-cerebellar-purkinje-cells
#12
Hyun Geun Shim, Dong Cheol Jang, Jaegeon Lee, Geehoon Chung, Sukchan Lee, Yong Gyu Kim, Da Eun Jeon, Sang Jeong Kim
Long-term depression (LTD) at parallel fibres (PF) to cerebellar Purkinje cells (PC) synapse is implicated in the output of PC, the sole output of the cerebellar cortex. Besides the synaptic plasticity, intrinsic excitability is also one of the components which determines the PC output. Although long-term potentiation of intrinsic excitability (LTP-IE) has been suggested, it has yet to be investigated how PF-PC LTD modifies intrinsic excitability of PC. Here, we show that pairing of the PF and climbing fibre (CF) for PF-PC LTD induction evokes long-term depression of intrinsic excitability (LTD-IE) in the cerebellar PCs from male C57BL/6 mice...
May 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#13
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...
July 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
#14
Amr A Mahrous, Sherif M Elbasiouny
Burst firing in motoneurons represents the basis for generating meaningful movements. Neuromodulators and inhibitory receptor blocker cocktails have been used for years to induce burst firing in vitro; however, the ionic mechanisms in the motoneuron membrane that contribute to burst initiation and amplitude modulation are not fully understood. Small conductance Ca(2+)-activated potassium (SK) channels regulate excitatory inputs and firing output of motoneurons and interneurons and therefore, are a candidate for mediating bursting behavior...
July 1, 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
#15
Angelo G Torrente, Rui Zhang, Heidi Wang, Audrey Zaini, Brian Kim, Xin Yue, Kenneth D Philipson, Joshua I Goldhaber
KEY POINTS: Repolarizing currents through K(+) channels are essential for proper sinoatrial node (SAN) pacemaking, but the influence of intracellular Ca(2+) on repolarization in the SAN is uncertain. We identified all three isoforms of Ca(2+) -activated small conductance K(+) (SK) channels in the murine SAN. SK channel blockade slows repolarization and subsequent depolarization of SAN cells. In the atrial-specific Na(+) /Ca(2+) exchanger (NCX) knockout mouse, cellular Ca(2+) accumulation during spontaneous SAN pacemaker activity produces intermittent hyperactivation of SK channels, leading to arrhythmic pauses alternating with bursts of pacing...
June 15, 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
#16
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
#17
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
#18
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
#19
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
#20
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
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