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voltage gated potassium channel

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https://www.readbyqxmd.com/read/29035780/long-non-coding-rnas-in-the-atherosclerotic-plaque
#1
Serdal Arslan, Öcal Berkan, Torkia Lalem, Nil Özbilüm, Sabahattin Göksel, Özge Korkmaz, Nilgün Çetin, Yvan Devaux
BACKGROUND AND AIMS: Genetic and environmental factors are important components of the development of atherosclerosis. Long non-coding RNA (lncRNAs) have emerged as regulators of multiple pathophysiological pathways in the cardiovascular system. Here, we investigated potential associations between lncRNAs and atherosclerosis. METHODS: Tissue samples from atherosclerotic coronary artery plaques and non-atherosclerotic internal mammary artery were obtained from 20 patients during coronary artery bypass surgery...
October 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29022505/pharmacological-targeting-of-neuronal-kv7-2-3-channels-a-focus-on-chemotypes-and-receptor-sites
#2
Francesco Miceli, Maria Virginia Soldovieri, Paolo Ambrosino, Laura Manocchio, Alessandro Medoro, Ilaria Mosca, Maurizio Taglialatela
BACKGROUND: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing a characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for development of new drugs for neuronal, cardiac and metabolic diseases. OBJECTIVE: In the present manuscript, we focus on describing the pharmacological relevance and the potential therapeutic applications of drugs acting on neuronally-expressed Kv7...
October 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29016852/potassium-channel-dysfunction-underlies-purkinje-neuron-spiking-abnormalities-in-spinocerebellar-ataxia-type-2
#3
James M Dell'Orco, Stefan M Pulst, Vikram G Shakkottai
Alterations in Purkinje neuron firing often accompany ataxia, but the molecular basis for these changes is poorly understood. In a mouse model of spinocerebellar ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing frequency accompanies cell atrophy. We investigated the basis for altered Purkinje neuron firing in SCA2. A reduction in the expression of large-conductance calcium-activated potassium (BK) channels and Kv3.3 voltage-gated potassium channels accompanies the inability of Purkinje neurons early in disease to maintain repetitive spiking...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28994652/mechanism-of-activation-at-the-selectivity-filter-of-the-kcsa-k-channel
#4
Florian T Heer, David J Posson, Wojciech Wojtas-Niziurski, Crina M Nimigean, Simon Bernèche
Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K(+) channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K(+) channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K(+) affinity, and increased ion permeation...
October 10, 2017: ELife
https://www.readbyqxmd.com/read/28993838/delta-opioid-receptor-expression-and-function-in-primary-afferent-somatosensory-neurons
#5
Amaury François, Grégory Scherrer
The functional diversity of primary afferent neurons of the dorsal root ganglia (DRG) generates a variety of qualitatively and quantitatively distinct somatosensory experiences, from shooting pain to pleasant touch. In recent years, the identification of dozens of genetic markers specifically expressed by subpopulations of DRG neurons has dramatically improved our understanding of this diversity and provided the tools to manipulate their activity and uncover their molecular identity and function. Opioid receptors have long been known to be expressed by discrete populations of DRG neurons, in which they regulate cell excitability and neurotransmitter release...
October 10, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28993277/structure-folding-and-stability-of-a-minimal-homologue-from-anemonia-sulcata-of-the-sea-anemone-potassium-channel-blocker-shk
#6
Bankala Krishnarjuna, Christopher A MacRaild, Punnepalli Sunanda, Rodrigo A V Morales, Steve Peigneur, Jason Macrander, Heidi H Yu, Marymegan Daly, Srinivasarao Raghothama, Vikas Dhawan, Satendra Chauhan, Jan Tytgat, Michael W Pennington, Raymond S Norton
Peptide toxins elaborated by sea anemones target various ion-channel sub-types. Recent transcriptomic studies of sea anemones have identified several novel candidate peptides, some of which have cysteine frameworks identical to those of previously reported sequences. One such peptide is AsK132958, which was identified in a transcriptomic study of Anemonia sulcata and has a cysteine framework similar to that of ShK from Stichodactyla helianthus, but is six amino acid residues shorter. We have determined the solution structure of this novel peptide using NMR spectroscopy...
October 6, 2017: Peptides
https://www.readbyqxmd.com/read/28992529/a-comprehensive-structural-model-for-the-human-kcnq1-kcne1-ion-channel
#7
Horia Jalily Hasani, Marawan Ahmed, Khaled Barakat
The voltage-gated KCNQ1/KCNE1 potassium ion channel complex, forms the slow delayed rectifier (IKs) current in the heart, which plays an important role in heart signaling. The importance of KCNQ1/KCNE1 channel's function is further implicated by the linkage between loss-of-function and gain-of-function mutations in KCNQ1 or KCNE1, and long QT syndromes, congenital atrial fibrillation, and short QT syndrome. Also, KCNQ1/KCNE1 channels are an off-target for many non-cardiovascular drugs, leading to fatal cardiac irregularities...
September 29, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28992433/kcnq-encoded-potassium-channels-as-therapeutic-targets
#8
Vincenzo Barrese, Jennifer B Stott, Iain A Greenwood
Kv7 channels are voltage-gated potassium channels encoded by KCNQ genes that have a considerable physiological impact in many cell types. This reliance upon Kv7 channels for normal cellular function, as well as the existence of hereditary disorders caused by mutations to KCNQ genes, means that pharmacological targeting of these channels has broad appeal. Consequently, a plethora of chemical entities that modulate Kv7 channel activity have been developed. Moreover, Kv7 channels are influenced by many disparate intracellular mediators and trafficking processes, making upstream targeting an appealing prospect for therapeutic development...
October 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28982705/sk-channels-regulate-resting-properties-and-signaling-reliability-of-a-developing-fast-spiking-neuron
#9
Yihui Zhang, Hai Huang
Reliable and precise signal transmission is essential in circuits of the auditory brainstem in order to encode timing with submillisecond accuracy. Globular bushy cells reliably and faithfully transfer spike signals to the principal neurons of the medial nucleus of the trapezoid body (MNTB) through the giant glutamatergic synapse, the calyx of Held. Thus, the MNTB works as a relay nucleus that preserves the temporal pattern of firing at high frequency. Using whole-cell patch-clamp recordings, we observed a K(+) conductance mediated by small-conductance calcium-activated potassium (SK) channels in the MNTB neurons from rats of either sex...
October 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28976052/kv7-potassium-channels-as-signal-transduction-intermediates-in-the-control-of-microvascular-tone
#10
Kenneth L Byron, Lyubov I Brueggemann
Potassium channels are recognized as important regulators of cellular functions in most, if not all cell types. These cellular proteins assemble to form gated pores in the plasma membrane, which serve to regulate the flow of potassium ions (K(+) ) from the cytosol to the extracellular space. In vascular smooth muscle cells (VSMCs), the open state of potassium channels enables the efflux of K(+) and thereby establishes a negative resting voltage across the plasma membrane that inhibits the opening of voltage-sensitive Ca(2+) channels (VSCCs)...
October 4, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28971158/scorpion-related-cardiomyopathy-and-acute-pulmonary-edema-in-a-child-who-is-stung-by-leiurus-abdullahbayrami
#11
Mehmet Dokur, Mustafa Dogan, Ersen Aydin Yagmur
Venom of Leiurus abdullahbayrami (Scorpiones: Buthidae) is an extremely toxic one and it stimulates voltage-gated sodium and potassium channels. In case of a stung by this scorpion; excessive catecholamine release occur and it impairs left ventricle contractility and consequently a heart failure occurs (scorpion sting-related cardiomyopathy). In addition to this cardiac-induced acute pulmonary, edema may occur in severe cases too. An 11-year-old male child who was stung by a scorpion (species: Leiurus abdullahbayrami) consulted to the Emergency Room...
September 2017: Turkish Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28970335/fusicoccin-activates-kat1-channels-by-stabilizing-their-interaction-with-14-3-3-proteins
#12
Andrea Saponaro, Alessandro Porro, Antonio Chaves-Sanjuan, Marco Nardini, Oliver Rauh, Gerhard Thiel, Anna Moroni
Plants acquire potassium (K+) ions for cell growth and movement via regulated diffusion through K+ channels. Here we present crystallographic and functional data showing that the K+ inward rectifier KAT1 channel is regulated by 14-3-3 proteins and further modulated by the phytotoxin fusicoccin, in analogy to the H+-ATPase. We identified a 14-3-3 mode III binding site at the very C-terminus of KAT1 and co-crystallized it with tobacco 14-3-3 proteins to describe the protein complex at atomic detail. Validation of this interaction by electrophysiology shows that 14-3-3 binding augments KAT1 conductance by increasing the maximal current and by positively shifting the voltage-dependency of gating...
September 29, 2017: Plant Cell
https://www.readbyqxmd.com/read/28968370/peripheral-nerve-hyperexcitability-syndromes
#13
Komal Sawlani, Bashar Katirji
PURPOSE OF REVIEW: This article provides a review of the clinical phenotypes and evaluation of peripheral nerve hyperexcitability syndromes. These rare diagnoses include cramp-fasciculation syndrome, Isaacs syndrome, and Morvan syndrome. Recent investigations have led to an understanding of the autoimmune underpinnings of these conditions and their specific associated antibodies. As the presentation of peripheral nerve hyperexcitability syndromes includes muscle stiffness, twitches, and spasms, which are also shared with certain central nervous system and myopathic conditions, the differential diagnosis of peripheral nerve hyperexcitability syndromes is reviewed...
October 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28968369/sensory-polyneuropathies
#14
Kelly Graham Gwathmey
PURPOSE OF REVIEW: This article describes the methods of diagnosis and management of the sensory-predominant polyneuropathies. To simplify the approach to this category of patients, sensory-predominant polyneuropathies are divided broadly into either small fiber (or pain-predominant) neuropathies and large fiber (or ataxia-predominant) neuropathies, of which the sensory neuronopathies (dorsal root ganglionopathies) are highlighted. RECENT FINDINGS: Physicians can now easily perform skin biopsies in their offices, allowing access to the gold standard pathologic diagnostic tool for small fiber neuropathies...
October 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28964116/revealing-kinetics-and-state-dependent-binding-properties-of-ikur-targeting-drugs-that-maximize-atrial-fibrillation-selectivity
#15
Nicholas Ellinwood, Dobromir Dobrev, Stefano Morotti, Eleonora Grandi
The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects...
September 2017: Chaos
https://www.readbyqxmd.com/read/28963344/structural-complexity-in-the-kctd-family-of-cullin3-dependent-e3-ubiquitin-ligases
#16
Daniel M Pinkas, Caroline E Sanvitale, Joshua C Bufton, Fiona J Sorrell, Nicolae Solcan, Rod Chalk, James Doutch, Alex N Bullock
Members of the potassium channel tetramerization domain (KCTD) family are soluble non-channel proteins that commonly function as Cullin3 (Cul3)-dependent E3 ligases. Solution studies of the N-terminal BTB domain have suggested that some KCTD family members may tetramerize similarly to the homologous tetramerization domain (T1) of the voltage-gated potassium (Kv) channels. However, available structures of KCTD1, KCTD5 and KCTD9 have demonstrated instead pentameric assemblies. To explore other phylogenetic clades within the KCTD family, we determined the crystal structures of the BTB domains of a further five human KCTD proteins revealing a rich variety of oligomerization architectures, including monomer (SHKBP1), a novel two-fold symmetric tetramer (KCTD10 and KCTD13), open pentamer (KCTD16) and closed pentamer (KCTD17)...
September 28, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28962160/effect-of-eicosapentaenoic-acid-and-pitavastatin-on-electrophysiology-and-anticoagulant-gene-expression-in-mice-with-rapid-atrial-pacing
#17
Maoqing Tong, Jiewen Wang, Yunxin Ji, Xiaomin Chen, Jieru Wang, Shuangshuang Wang, Liemin Ruan, Hanbin Cui, Ying Zhou, Qingyu Zhang, Eiichi Watanabe
Atrial remodeling is considered to be any persistent change in atrial structure or function, and is responsible for the development and perpetuation of atrial fibrillation (AF). Oxidative stress and intracellular pH regulation may also be linked to AF; however it remains unclear whether eicosapentaenoic acid (EPA) or statins have beneficial therapeutic effects. The aim of the present study was to investigate the effects of EPA and pitavastatin on the electrophysiology of and gene expressions in mice with rapidly-paced atria...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28943756/slick-kcnt2-sodium-activated-potassium-channels-limit-peptidergic-nociceptor-excitability-and-hyperalgesia
#18
Danielle L Tomasello, Edward Hurley, Lawrence Wrabetz, Arin Bhattacharjee
The Slick (Kcnt2) sodium-activated potassium (KNa) channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs), we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene-related peptide (CGRP)-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV)-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane...
2017: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/28940182/bk-%C3%AE-1-subunit-dependent-facilitation-of-ethanol-inhibition-of-bk-current-and-cerebral-artery-constriction-is-mediated-by-the-%C3%AE-1-transmembrane-domain-2
#19
Guruprasad Kuntamallappanavar, Alex M Dopico
BACKGROUND AND PURPOSE: Ethanol at concentrations obtained in circulation during moderate-heavy episodic drinking (30-60 mM) causes cerebral artery constriction in several species, including humans. In rodents, ethanol-induced cerebral artery constriction results from ethanol inhibition of large conductance voltage/Ca(2+)i -gated potassium (BK) channels in cerebral artery myocytes. Moreover, the smooth muscle-abundant BK β1 accessory subunit is required for ethanol to inhibit cerebral artery myocyte BK channels under physiological Ca(2+)i and voltages, and thus constrict cerebral arteries...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28936074/syndromes-of-rapidly-progressive-cognitive-decline-our-experience
#20
Sadanandavalli Retnaswami Chandra, Lakshminarayanapuram Gopal Viswanathan, Anupama Ramakanth Pai, Rahul Wahatule, Suvarna Alladi
BACKGROUND: Dementias are fairly slowly progressive degenerative diseases of brain for which treatment options are very less and carry a lot of burden on family and society. A small percentage of them are rapidly progressive and mostly carry a different course outcome. However, there are no definite criteria other than the time line for these patients. AIMS: The aim of this was to identify and categorize the causes and course of rapidly progressive dementias seen in our center...
August 2017: Journal of Neurosciences in Rural Practice
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