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The focal adhesion protein Testin modulates KCNE2 potassium channel β subunit activity Channels (IF 2.311) Pub Date : 2021-01-19 Maria Papanikolaou; Shawn M. Crump; Geoffrey W. Abbott
ABSTRACT Coronary Artery Disease (CAD) typically kills more people globally each year than any other single cause of death. A better understanding of genetic predisposition to CAD and the underlying mechanisms will help to identify those most at risk and contribute to improved therapeutic approaches. KCNE2 is a functionally versatile, ubiquitously expressed potassium channel β subunit associated with
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The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells Channels (IF 2.311) Pub Date : 2021-01-19 Dieter V. Van de Sande; Ivan Kopljar; Alaerts Maaike; Ard Teisman; David J. Gallacher; Loeys Bart; Dirk J. Snyders; Luc Leybaert; Hua Rong Lu; Alain J. Labro
ABSTRACT Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression
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TRPM2 in ischemic stroke: Structure, molecular mechanisms, and drug intervention Channels (IF 2.311) Pub Date : 2021-01-18 Qing Wang; Ning Liu; Yuan-Shu Ni; Jia-Mei Yang; Lin Ma; Xiao-Bing Lan; Jing Wu; Jian-Guo Niu; Jian-Qiang Yu
ABSTRACT Ischemic stroke has a high lethality rate worldwide, and novel treatments are limited. Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Transient receptor potential melastatin 2 (TRPM2) is a reactive oxygen species (ROS)-sensitive calcium channel. Cerebral ischemia-induced TRPM2 activation triggers abnormal intracellular Ca2+ accumulation and cell death, which
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Changes in peripheral HCN2 channels during persistent inflammation Channels (IF 2.311) Pub Date : 2021-01-11 L-A. R. Jansen; L. A. Forster; X. L. Smith; M. Rubaharan; A. Z. Murphy; D. J. Baro
ABSTRACT Nociceptor sensitization following nerve injury or inflammation leads to chronic pain. An increase in the nociceptor hyperpolarization-activated current, Ih, is observed in many models of pathological pain. Pharmacological blockade of Ih prevents the mechanical and thermal hypersensitivity that occurs during pathological pain. Alterations in the Hyperpolarization-activated Cyclic Nucleotide-gated
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Selective Targeting of Nav1.7 with Engineered Spider Venom-Based Peptides Channels (IF 2.311) Pub Date : 2021-01-11 Robert A. Neff; Alan D. Wickenden
ABSTRACT A fundamental mechanism that drives the propagation of electrical signals in the nervous system is the activation of voltage-gated sodium channels. The sodium channel subtype Nav1.7 is critical for the transmission of pain-related signaling, with gain-of-function mutations in Nav1.7 resulting in various painful pathologies. Loss-of-function mutations cause complete insensitivity to pain and
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Comparison of quinazoline and benzoylpyrazoline chemotypes targeting the CaVα-β interaction as antagonists of the N-type CaV2.2 channel Channels (IF 2.311) Pub Date : 2021-01-08 Dongzhi Ran; Kimberly Gomez; Aubin Moutal; Marcel Patek; Samantha Perez-Miller; Rajesh Khanna
ABSTRACT Structural studies with an α subunit fragment of voltage-gated calcium (CaV) channels in complex with the CaVβ subunits revealed a high homology between the various CaVα-β subunits, predicting that targeting of this interface would result in nonselective compounds. Despite this likelihood, my laboratory initiated a rational structure-based screening campaign focusing on “hot spots” on the
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Epigenetic control of ion channel expression and cell-specific splicing in nociceptors: Chronic pain mechanisms and potential therapeutic targets Channels (IF 2.311) Pub Date : 2021-01-08 Diane Lipscombe; E. Javier Lopez-Soto
ABSTRACT Ion channels underlie all forms for electrical signaling including the transmission of information about harmful events. Voltage-gated calcium ion channels have dual function, they support electrical signaling as well as intracellular calcium signaling through excitation-dependent calcium entry across the plasma membrane. Mechanisms that regulate ion channel forms and actions are essential
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Acid-sensing ion channel 3: An analgesic target Channels (IF 2.311) Pub Date : 2021-01-04 Jasdip Singh Dulai; Ewan St. John Smith; Taufiq Rahman
ABSTRACT Acid-sensing ion channel 3 (ASIC3) belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. There are 7 different ASIC subunits encoded by 5 different genes. Most ASIC subunits form trimeric ion channels that upon activation by extracellular protons mediate a transient inward current inducing cellular excitability. ASIC subunits exhibit differential tissue expression and
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Stabilization of negative activation voltages of Cav1.3 L-Type Ca2+-channels by alternative splicing Channels (IF 2.311) Pub Date : 2020-12-31 Nadja T. Hofer; Alexandra Pinggera; Yuliia V. Nikonishyna; Petronel Tuluc; Eva M. Fritz; Gerald J. Obermair; Jörg Striessnig
ABSTRACT -->Low voltage-activated Cav1.3 L-type Ca2+-channels are key regulators of neuronal excitability controlling neuronal development and different types of learning and memory. Their physiological functions are enabled by their negative activation voltage-range, which allows Cav1.3 to be active at subthreshold voltages. Alternative splicing in the C-terminus of their pore-forming α1-subunits
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Functional modulation of the human voltage-gated sodium channel NaV1.8 by auxiliary β subunits Channels (IF 2.311) Pub Date : 2020-12-29 S. T. Nevin; N. Lawrence; A. Nicke; R. J. Lewis; D. J. Adams
ABSTRACT The voltage-gated sodium channel Nav1.8 mediates the tetrodotoxin-resistant (TTX-R) Na+ current in nociceptive primary sensory neurons, which has an important role in the transmission of painful stimuli. Here, we describe the functional modulation of the human Nav1.8 α-subunit in Xenopus oocytes by auxiliary β subunits. We found that the β3 subunit down-regulated the maximal Na+ current amplitude
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Immunomagnetic separation is a suitable method for electrophysiology and ion channel pharmacology studies on T cells Channels (IF 2.311) Pub Date : 2020-12-28 Gabor Tajti; Tibor Gabor Szanto; Agota Csoti; Greta Racz; César Evaristo; Peter Hajdu; Gyorgy Panyi
ABSTRACT Ion channels play pivotal role in the physiological and pathological function of immune cells. As immune cells represent a functionally diverse population, subtype-specific functional studies, such as single-cell electrophysiology require proper subset identification and separation. Magnetic-activated cell sorting (MACS) techniques provide an alternative to fluorescence-activated cell sorting
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Kv1.3 inhibition attenuates neuroinflammation through disruption of microglial calcium signaling Channels (IF 2.311) Pub Date : 2020-12-28 Alla F. Fomina; Hai M. Nguyen; Heike Wulff
ABSTRACT In the last 5 years inhibitors of the potassium channel KV1.3 have been shown to reduce neuroinflammation in rodent models of ischemic stroke, Alzheimer’s disease, Parkinson’s disease and traumatic brain injury. At the systemic level these beneficial actions are mediated by a reduction in microglia activation and a suppression of pro-inflammatory cytokine and nitric oxide production. However
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Trigeminal neuropathic pain is alleviated by inhibition of Cav3.3 T-type calcium channels in mice Channels (IF 2.311) Pub Date : 2020-12-23 Marena Montera; Aleyah Goins; Leos Cmarko; Norbert Weiss; Karin N. Westlund; Sascha R. A. Alles
ABSTRACT In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Cav3.3 compared
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Late sodium current and calcium homeostasis in arrhythmogenesis Channels (IF 2.311) Pub Date : 2020-12-21 Kornél Kistamás; Tamás Hézső; Balázs Horváth; Péter P Nánási
ABSTRACT The cardiac late sodium current (INa,late) is the small sustained component of the sodium current active during the plateau phase of the action potential. Several studies demonstrated that augmentation of the current can lead to cardiac arrhythmias; therefore, INa,late is considered as a promising antiarrhythmic target. Fundamentally, enlarged INa,late increases Na+ influx into the cell, which
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The clinical and genetic heterogeneity analysis of five families with primary periodic paralysis Channels (IF 2.311) Pub Date : 2020-12-21 Quanquan Wang; Zhe Zhao; Hongrui Shen; Qi Bing; Nan Li; Jing Hu
ABSTRACT To explore the clinical and genetic characteristics of five families with primary periodic paralysis (PPP). We reviewed clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, and genetic analysis from five families with PPP. Five families with PPP included: hypokalemic periodic paralysis type 1 (HypoPP1, CACNA1S, 1/5), hypokalemic periodic paralysis
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Trigeminal neuropathic pain is alleviated by inhibition of Cav3.3 T-type calcium channels in mice Channels (IF 2.311) Pub Date : 2020-12-07 Marena Montera; Aleyah Goins; Leos Cmarko; Norbert Weiss; Karin N. Westlund High; Sascha R.A. Alles
Abstract In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Cav3.3 compared
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The cool things to know about TRPM8! Channels (IF 2.311) Pub Date : 2020-11-04 Mircea Iftinca; Christophe Altier
ABSTRACT Transient receptor potential melastatin 8 (TRPM8) channels play a central role in the detection of environmental cold temperatures in the somatosensory system. TRPM8 is found in a subset of unmyelinated (C-type) afferents located in the dorsal root (DRG) and trigeminal ganglion (TG). Cold hypersensitivity is a common symptom of neuropathic pain conditions caused by cancer therapy, spinal cord
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Bibliometric analysis of chloride channel research (2004–2019) Channels (IF 2.311) Pub Date : 2020-10-24 Jingjing Shi; Shuqing Shi; Guozhen Yuan; QiuLei Jia; Shuai Shi; Xueping Zhu; Yan Zhou; Ting Chen; Yuanhui Hu
(2020). Bibliometric analysis of chloride channel research (2004–2019) Channels: Vol. 14, No. 1, pp. 393-402.
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Similarities between the effect of SARS-CoV-2 and HCV on the cellular level, and the possible role of ion channels in COVID19 progression: a review of potential targets for diagnosis and treatment Channels (IF 2.311) Pub Date : 2020-10-22 Hani Alothaid; Mohammed S. K. Aldughaim; Karim El Bakkouri; Sufana AlMashhadi; Ahmed A. Al-Qahtani
ABSTRACT The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted an urgent need to identify effective medicines for the prevention and treatment of the disease. A comparative analysis between SARS-CoV-2 and Hepatitis C Virus (HCV) can expand the available knowledge regarding the virology and potential drug targets against these viruses. Interestingly
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Cav2.3 channel function and Zn2+-induced modulation: potential mechanisms and (patho)physiological relevance Channels (IF 2.311) Pub Date : 2020-10-20 Felix Neumaier; Toni Schneider; Walid Albanna
ABSTRACT Voltage-gated calcium channels (VGCCs) are critical for Ca2+ influx into all types of excitable cells, but their exact function is still poorly understood. Recent reconstruction of homology models for all human VGCCs at atomic resolution provides the opportunity for a structure-based discussion of VGCC function and novel insights into the mechanisms underlying Ca2+ selective flux through these
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Modulation of voltage-gated CaV2.2 Ca2+ channels by newly identified interaction partners Channels (IF 2.311) Pub Date : 2020-10-15 Lubica Lacinova; Robert Theodor Mallmann; Bohumila Jurkovičová-Tarabová; Norbert Klugbauer
ABSTRACT Voltage-gated Ca2+ channels are typically integrated in a complex network of protein-protein-interactions, also referred to as Ca2+ channel nanodomains. Amongst the neuronal CaV2 channel family, CaV2.2 is of particular importance due to its general role for signal transmission from the periphery to the central nervous system, but also due to its significance for pain perception. Thus, CaV2
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Experimental induction and mathematical modeling of Ca 2+ dynamics in rat round spermatids Channels (IF 2.311) Pub Date : 2020-10-07 Jonathan Saavedra; Juan G. Reyes; Dino G. Salinas
ABSTRACT Cytosolic Ca2+ concentration ([Ca2+ ]) has an important role in spermatozoa and hence it regulates fertilization. In male germinal cells, there are indirect evidences that this ion could regulate physiological processes in spermatogenesis. Since little is known about Ca 2+ homeostasis in spermatogenic cells, in this work we propose a mathematical model that accounts for experimental [Ca2+
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Analysis of Arabidopsis TPK2 and KCO3 reveals structural properties required for K+ channel function Channels (IF 2.311) Pub Date : 2020-10-04 Chihiro Uehara; Kota Takeda; Tatsuki Ibuki; Tadaomi Furuta; Naomi Hoshi; Ellen Tanudjaja; Nobuyuki Uozumi
ABSTRACT Arabidopsis thaliana contains five tandem-pore domain potassium channels, TPK1-TPK5 and the related one-pore domain potassium channel, KCO3. Although KCO3 is unlikely to be an active channel, it still has a physiological role in plant cells. TPK2 is most similar to KCO3 and both are localized to the tonoplast. However, their function remains poorly understood. Here, taking advantage of the
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Charged pore-lining residues are required for normal channel kinetics in the eukaryotic mechanosensitive ion channel MSL1 Channels (IF 2.311) Pub Date : 2020-09-29 Angela M. Schlegel; Elizabeth S. Haswell
ABSTRACT Mechanosensitive (MS) ion channels are widespread mechanisms for cellular mechanosensation that can be directly activated by increasing membrane tension. The well-studied MscS family of MS ion channels is found in bacteria, archaea, and plants. MscS-Like (MSL)1 is localized to the inner mitochondrial membrane of Arabidopsis thaliana, where it is required for normal mitochondrial responses
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Modulation of Ca2+-induced Ca2+ release by ubiquitin protein ligase E3 component n-recognin UBR3 and 6 in cardiac myocytes Channels (IF 2.311) Pub Date : 2020-09-29 Xiu-E Ma; Bei Liu; Chun-Xia Zhao
ABSTRACT Ca2+-induced Ca2+ release (CICR) from sarcoplasmic reticulum is a finely tuned process responsible for cardiac excitation and contraction. The ubiquitin–proteasome system (UPS) as a major degradative system plays a crucial role in the maintenance of Ca2+ homeostasis. The E3 component N-recognin (UBR) subfamily is a part of the UPS; however, the role of UBR in regulating cardiac CICR is unknown
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Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains. Channels (IF 2.311) Pub Date : 2020-09-12 Sara J Codding,Ashley A Johnson,Matthew C Trudeau
The KCNH family comprises the ERG, EAG, and ELK voltage-activated, potassium-selective channels. Distinct from other K channels, KCNH channels contain unique structural domains, including a PAS (Per-Arnt-Sim) domain in the N-terminal region and a CNBHD (cyclic nucleotide-binding homology domain) in the C-terminal region. The intracellular PAS domains and CNBHDs interact directly and regulate some of
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Calmodulin binds to the N-terminal domain of the cardiac sodium channel Nav1.5. Channels (IF 2.311) Pub Date : 2020-08-20 Zizun Wang,Sarah H Vermij,Valentin Sottas,Anna Shestak,Daniela Ross-Kaschitza,Elena V Zaklyazminskaya,Andy Hudmon,Geoffrey S Pitt,Jean-Sébastien Rougier,Hugues Abriel
ABSTRACT The cardiac voltage-gated sodium channel Nav1.5 conducts the rapid inward sodium current crucial for cardiomyocyte excitability. Loss-of-function mutations in its gene SCN5A are linked to cardiac arrhythmias such as Brugada Syndrome (BrS). Several BrS-associated mutations in the Nav1.5 N-terminal domain (NTD) exert a dominant-negative effect (DNE) on wild-type channel function, for which mechanisms
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Loss of Cav1.2 channels impairs hippocampal theta burst stimulation-induced long-term potentiation Channels (IF 2.311) Pub Date : 2020-08-15 Preethy S. Sridharan; Yuan Lu; Richard C Rice; Andrew A. Pieper; Anjali M. Rajadhyaksha
ABSTRACT CACNA1 C, which codes for the Cav1.2 isoform of L-type Ca2+ channels (LTCCs), is a prominent risk gene in neuropsychiatric and neurodegenerative conditions. A role forLTCCs, and Cav1.2 in particular, in transcription-dependent late long-term potentiation (LTP) has long been known. Here, we report that elimination of Cav1.2 channels in glutamatergic neurons also impairs theta burst stimulation
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Polymodal roles of TRPC3 channel in the kidney Channels (IF 2.311) Pub Date : 2020-08-12 Naghmeh Hassanzadeh Khayyat; Viktor N. Tomilin; Oleg Zaika; Oleh Pochynyuk
ABSTRACT TRPC3 is a Ca2+-permeable cation channel commonly activated by the G-protein coupled receptors (GPCR) and mechanical distortion of the plasma membrane. TRPC3-mediated Ca2+ influx has been implicated in a variety of signaling processes in both excitable and non-excitable cells. Kidneys play a commanding role in maintaining whole-body homeostasis and setting blood pressure. TRPC3 is expressed
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Gap junctions amplify TRPV4 activation-initiated cell injury via modification of intracellular Ca2+ and Ca2+-dependent regulation of TXNIP. Channels (IF 2.311) Pub Date : 2020-08-04 Xiling Zhang,Zhimin Mao,Yanru Huang,Zhen Zhang,Jian Yao
ABSTRACT The elevated intracellular Ca2+ and oxidative stress are well-reported mechanisms behind renal tubular epithelial injury initiated by various insults. Given that TRPV4 and connexin43 (Cx43) channels are activated by a wide range of stimuli and regulate both intracellular Ca2+ and redox status, we speculated an involvement of these channels in renal tubular cell injury. Here, we tested this
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A low voltage activated Ca2+ current found in a subset of human ventricular myocytes. Channels (IF 2.311) Pub Date : 2020-07-20 Xin Zhang,Yijia Li,Xiaoying Zhang,Valentino Piacentino,David M Harris,Remus Berretta,Kenneth B Margulies,Steven R Houser,Xiongwen Chen
ABSTRACT Low voltage activated (ICa-LVA) calcium currents including Cav1.3 and T-type calcium current (ICa-T) have not been reported in adult human left ventricular myocytes (HLVMs). We tried to examine their existence and possible correlation with etiology and patient characteristics in a big number of human LVMs isolated from explanted terminally failing (F) hearts, failing hearts with left ventricular
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Bibliometric analysis of calcium channel research (2010-2019). Channels (IF 2.311) Pub Date : 2020-07-13 Jingjing Shi,Huan Wang,Shuqing Shi,Guozhen Yuan,QiuLei Jia,Shuai Shi,Xuesong Zhang,Yuanhui Hu
ABSTRACT Calcium channels are involved in pathologies across all the major therapeutic areas involving the cardiac, neurological, metabolic, and respiratory systems. Although calcium channels have been the hotspot of multidisciplinary research for decades, the hotspots and frontier trends of calcium channel research have not been comprehensively analyzed by bibliometrics. Here, we collected scientific
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Sphingosine kinase 2 inhibitor ABC294640 suppresses neuronal excitability and inhibits multiple endogenously and exogenously expressed voltage-gated ion channels in cultured cells. Channels (IF 2.311) Pub Date : 2020-07-13 Fei Zhang,Wenqi Hu,Lili Qu,Chunlei Cang
ABSTRACT Sphingolipids regulate multiple cellular processes, including proliferation, autophagy, and apoptosis. Sphingosine kinases, the key enzymes in the metabolism of sphingolipids, are overexpressed in many cancers, making them important targets for the development of antitumor drugs. ABC294640 is a selective sphingosine kinase 2 (SK2) inhibitor that shows good antitumor activity in vitro. One
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A bibliometric analysis and review of recent researches on TRPM7. Channels (IF 2.311) Pub Date : 2020-07-09 Shiqi Zhang,Dongyi Zhao,Wanying Jia,Yuting Wang,Hongyue Liang,Lei Liu,Wuyang Wang,Zhiyi Yu,Feng Guo
ABSTRACT The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed protein that contains both an ion channel and an active kinase. TRPM7 has involved in a variety of cellular functions and critically participates in various diseases mainly including cancer and neurodegenerative disorders. However, the theme trends and knowledge structures for TRPM7 have not
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The Slo3/Lrrc52 complex is sensitive to phosphoinositides. Channels (IF 2.311) Pub Date : 2020-06-21 Takafumi Kawai,Yasushi Okamura
ABSTRACT The voltage-sensing phosphatase (VSP) is a unique protein that shows voltage-dependent phosphatase activity toward phosphoinositides. Recently, we reported that VSP is activated and generates polarized PtdIns(4,5)P2 distribution in sperm flagellum. Interestingly, such specialized PtdIns(4,5)P2 distribution appears to contribute to the activity of Slo3, a sperm-specific K+ channels. It has
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The effect of MD1 on potassium and L-type calcium current of cardiomyocytes from high-fat diet mice. Channels (IF 2.311) Pub Date : 2020-06-03 Wei Shuai,Bin Kong,Hui Fu,Xiaobo Jiang,He Huang
ABSTRACT Myeloid differentiation protein 1 (MD1) is exerted an anti-arrhythmic effect in obese mice. Therefore, we sought to clarify whether MD1 can alter the electrophysiological remodeling of cardiac myocytes from obese mice by regulating voltage-gated potassium current and calcium current. MD1 knock-out (KO) and wild type (WT) mice were given a high-fat diet (HFD) for 20 weeks, starting at the age
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A de novo CACNA1D missense mutation in a patient with congenital hyperinsulinism, primary hyperaldosteronism and hypotonia. Channels (IF 2.311) Pub Date : 2020-05-04 María Carmen De Mingo Alemany,Luis Mifsud Grau,Francisca Moreno Macián,Belén Ferrer Lorente,Sara León Cariñena
Congenital hyperinsulinemic hypoglycemia is the most frequent cause of persistent and recurrent hypoglycemia in the first years of life and in many patients rare genetic variants can be identified. Recently a case of congenital hyperinsulinemic hypoglycemia and a severe neurodevelopmental syndrome due to a mutation in the voltage-gated Cav1.3 Ca2+ channel CACNA1D gene has been reported which required
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The mutation L69P in the PAS domain of the hERG potassium channel results in LQTS by trafficking deficiency. Channels (IF 2.311) Pub Date : 2020-04-17 Tina Jenewein,Scott A Kanner,Daniel Bauer,Brigitte Hertel,Henry M Colecraft,Anna Moroni,Gerhard Thiel,Silke Kauferstein
The congenital long QT syndrome (LQTS) is a cardiac disorder characterized by a prolonged QT interval on the electrocardiogram and an increased susceptibility to ventricular arrhythmias and sudden cardiac death. A frequent cause for LQTS is mutations in the KCNH2 gene (also known as the human ether-a-go-go-related gene or hERG), which reduce or modulate the potassium current IKr and hence alter cardiac
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The CaMKII phosphorylation site Thr1604 in the CaV1.2 channel is involved in pathological myocardial hypertrophy in rats. Channels (IF 2.311) Pub Date : 2020-04-14 Jingyuan Li,Siqi Wang,Jie Zhang,Yan Liu,Xi Zheng,Fan Ding,Xuefei Sun,Meimi Zhao,Liying Hao
Residue Thr1604 in the CaV1.2 channel is a Ca2+/calmodulin dependent protein kinase II (CaMKII) phosphorylation site, and its phosphorylation status maintains the basic activity of the channel. However, the role of CaV1.2 phosphorylation at Thr1604 in myocardial hypertrophy is incompletely understood. Isoproterenol (ISO) was used to induce cardiomyocyte hypertrophy, and autocamtide-2-related inhibitory
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The role of TRPV1 channels in atherosclerosis. Channels (IF 2.311) Pub Date : 2020-04-11 Chenyang Zhang,Lifang Ye,Qinggang Zhang,Fei Wu,Lihong Wang
Transient receptor potential vanilloid subfamily member 1 (TRPV1) is a nonselective cation channel, that is mainly distributed in sensory nerve endings and can release a variety of neurotransmitters after activation. Early studies showed that it mainly conducts pain sensation, but research has demonstrated that it also plays an important role in cardiovascular diseases. Notably, in atherosclerosis
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Transcriptomic analysis of glycan-processing genes in the dorsal root ganglia of diabetic mice and functional characterization on Cav3.2 channels. Channels (IF 2.311) Pub Date : 2020-04-03 Robin N Stringer,Joanna Lazniewska,Norbert Weiss
Cav3.2 T-type calcium channels play an essential role in the transmission of peripheral nociception in the dorsal root ganglia (DRG) and alteration of Cav3.2 expression is associated with the development of peripheral painful diabetic neuropathy (PDN). Several studies have previously documented the role of glycosylation in the expression and functioning of Cav3.2 and suggested that altered glycosylation
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The quest to identify the mechanism underlying adrenergic regulation of cardiac Ca2+ channels. Channels (IF 2.311) Pub Date : 2020-03-21 Daniel Roybal,Jessica A Hennessey,Steven O Marx
Activation of protein kinase A by cyclic AMP results in a multi-fold upregulation of CaV1.2 currents in the heart, as originally reported in the 1970's and 1980's. Despite considerable interest and much investment, the molecular mechanisms responsible for this signature modulation remained stubbornly elusive for over 40 years. A key manifestation of this lack of understanding is that while this regulation
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The structure and function of TRIP8b, an auxiliary subunit of hyperpolarization-activated cyclic-nucleotide gated channels. Channels (IF 2.311) Pub Date : 2020-03-20 Ye Han,Kyle A Lyman,Kendall M Foote,Dane M Chetkovich
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed throughout the mammalian central nervous system (CNS). These channels have been implicated in a wide range of diseases, including Major Depressive Disorder and multiple subtypes of epilepsy. The diversity of functions that HCN channels perform is in part attributable to differences in their subcellular localization. To
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Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells. Channels (IF 2.311) Pub Date : 2020-03-19 Atousa Arbabian,Mircea Iftinca,Christophe Altier,Param Priya Singh,Hervé Isambert,Sylvie Coscoy
Transient receptor potential (TRP) channels form a family of polymodal cation channels gated by thermal, mechanical, or chemical stimuli, with many of them involved in the control of proliferation, apoptosis, or cell cycle. From an evolutionary point of view, TRP family is characterized by high conservation of duplicated genes originating from whole-genome duplication at the onset of vertebrates. The
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T-type channels in neuropathic pain - Villain or victim? Channels (IF 2.311) Pub Date : 2020-03-14 Norbert Weiss
(2020). T-type channels in neuropathic pain - Villain or victim? Channels: Vol. 14, No. 1, pp. 98-100.
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Obtaining transition rates from single-channel data without initial parameter seeding. Channels (IF 2.311) Pub Date : 2020-02-29 Michael Voldsgaard Clausen
Background and Purpose: Ion-channels are membrane proteins that can adopt several distinct structural conformations. Some of the conformations are open and allow the passage of ions through the membrane; others are closed and hinder ion flow. Patch-clamp recordings of single ion-channels show if a channel is open or closed, but does not immediately reveal the underlying mechanism, which typically includes
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Regulation of the cold-sensing TRPM8 channels by phosphoinositides and Gq-coupled receptors. Channels (IF 2.311) Pub Date : 2020-02-27 Luyu Liu,Tibor Rohacs
The Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is an important sensor of environmental cold temperatures. Cold- and menthol-induced activation of this channel requires the presence of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. This review discusses recent findings on the role of PI(4,5)P2 and G-proteins in the modulation of TRPM8 upon receptor activation
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Activating Sirt1 by resveratrol suppresses Nav1.7 expression in DRG through miR-182 and alleviates neuropathic pain in rats. Channels (IF 2.311) Pub Date : 2020-02-22 Qianqian Jia,Wenze Dong,Liwei Zhang,Xiaochun Yang
Neuropathic pain is clinically unsatisfactorily treated because of unclear mechanisms. The present study aims to explore the concrete mechanisms underlying the alleviation of resveratrol-activated silent information regulator 1 (Sirt1) to chronic constriction injury (CCI)-induced neuropathic pain. CCI surgery was conducted to the unilateral sciatic nerve of male Sprague-Dawley rats to induce neuropathic
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TRPV1 inhibits smooth muscle cell phenotype switching in a mouse model of abdominal aortic aneurysm. Channels (IF 2.311) Pub Date : 2020-02-21 Shuo Wang,Chenhong Jia
The natural outcome of abdominal aortic aneurysm (AAA) is that of slow progression and ultimate rupture, then a life-threatening hemorrhage consequently. Ruptured AAA is a dramatic catastrophe and constitutes one of the leading causes of acute death in elderly men. However, the mechanism of AAA is still unclear. Transient receptor potential vanilloid (TRPV) family has protective effects in cardiovascular
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PAC proton-activated chloride channel contributes to acid-induced cell death in primary rat cortical neurons. Channels (IF 2.311) Pub Date : 2020-02-26 James Osei-Owusu,Junhua Yang,Maria Del Carmen Vitery,Mengnan Tian,Zhaozhu Qiu
Severe local acidosis causes tissue damage and pain, and is associated with many diseases, including cerebral and cardiac ischemia, cancer, infection, and inflammation. However, the molecular mechanisms of the cellular response to extracellular acidic environment are not fully understood. We recently identified a novel and evolutionarily conserved membrane protein, PAC (also known as PACC1 or TMEM206)
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Flow fluorometry quantification of anion channel VRAC subunit LRRC8A at the membrane of living U937 cells. Channels (IF 2.311) Pub Date : 2020-02-20 Valentina Yurinskaya,Nikolay Aksenov,Alexey Moshkov,Tatyana Goryachaya,Ashley Shemery,Alexey Vereninov
Assessing the expression of channels on the cell membrane is a necessary step in studying the functioning of ion channels in living cells. We explore, first, if endogenous VRAC can be assayed using flow cytometry and a commercially available antibody against an extracellular loop of the LRRC8A, also known as SWELL1, subunit of the VRAC channel. The second goal is to determine if an increase in the
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TRAM1 protein may support ER protein import by modulating the phospholipid bilayer near the lateral gate of the Sec61-channel. Channels (IF 2.311) Pub Date : 2020-02-11 Marie-Christine Klein,Monika Lerner,Duy Nguyen,Stefan Pfeffer,Johanna Dudek,Friedrich Förster,Volkhard Helms,Sven Lang,Richard Zimmermann
In mammalian cells, one-third of all polypeptides is transported into or through the ER-membrane via the Sec61-channel. While the Sec61-complex facilitates the transport of all polypeptides with amino-terminal signal peptides (SP) or SP-equivalent transmembrane helices (TMH), the translocating chain-associated membrane protein (now termed TRAM1) was proposed to support transport of a subset of precursors
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Bibliometric analysis of potassium channel research Channels (IF 2.311) Pub Date : 2019-12-19 Jingjing Shi; Shuqing Shi; Shuai Shi; Qiulei Jia; Guozhen Yuan; Yuguang Chu; Huan Wang; Yuanhui Hu; Hanming Cui
ABSTRACT ABSTRACT Objective: To explore the research status, hotspots, and trends in research on potassium channel. Methods: The Web of Science core collection database was used as the data source and the visual analysis software Citespace5.4 R3 was used to visualize the studies of potassium channel in the past 10 years. The national/institutional distribution, journal distribution, authors, and related
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Trafficking mechanisms underlying Nav channel subcellular localization in neurons Channels (IF 2.311) Pub Date : 2019-12-14 Laura Solé; Michael M. Tamkun
ABSTRACT Voltage gated sodium channels (Nav) play a crucial role in action potential initiation and propagation. Although the discovery of Nav channels dates back more than 65 years, and great advances in understanding their localization, biophysical properties, and links to disease have been made, there are still many questions to be answered regarding the cellular and molecular mechanisms involved
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Elementary calcium signaling in arterial smooth muscle Channels (IF 2.311) Pub Date : 2019-12-04 Gang Fan, Yingqiu Cui, Maik Gollasch, Mario Kassmann
Vascular smooth muscle cells (VSMCs) of small peripheral arteries contribute to blood pressure control by adapting their contractile state. These adaptations depend on the VSMC cytosolic Ca2+ concentration, regulated by complex local elementary Ca2+ signaling pathways. Ca2+ sparks represent local, transient, rapid calcium release events from a cluster of ryanodine receptors (RyRs) in the sarcoplasmic
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PI3Kα in cardioprotection: Cytoskeleton, late Na+ current, and mechanism of arrhythmias. Channels (IF 2.311) Pub Date : 2019-12-02 Pavel Zhabyeyev,Xueyi Chen,Bart Vanhaesebroeck,Gavin Y Oudit
PI 3-kinase α (PI3Kα) is a lipid kinase that converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3). PI3Kα regulates a variety of cellular processes such as nutrient sensing, cell cycle, migration, and others. Heightened activity of PI3Kα in many types of cancer made it a prime oncology drug target, but also raises concerns of possible adverse effects
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A conserved arginine/lysine-based motif promotes ER export of KCNE1 and KCNE2 to regulate KCNQ1 channel activity. Channels (IF 2.311) Pub Date : 2019-11-03 Bin Hu,Wen-Ping Zeng,Xia Li,Umar Al-Sheikh,San-You Chen,Jiuping Ding
KCNE β-subunits play critical roles in modulating cardiac voltage-gated potassium channels. Among them, KCNE1 associates with KCNQ1 channel to confer a slow-activated IKs current, while KCNE2 functions as a dominant negative modulator to suppress the current amplitude of KCNQ1. Any anomaly in these channels will lead to serious myocardial diseases, such as the long QT syndrome (LQTS). Trafficking defects
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Evaluation of edonerpic maleate as a CRMP2 inhibitor for pain relief. Channels (IF 2.311) Pub Date : 2019-11-02 Aubin Moutal,Zhiming Shan,Victor G Miranda,Liberty François-Moutal,Cynthia L Madura,May Khanna,Rajesh Khanna
We have previously reported that the microtubule-associated collapsin response mediator protein 2 (CRMP2) is necessary for the expression of chronic pain. CRMP2 achieves this control of nociceptive signaling by virtue of its ability to regulate voltage-gated calcium and sodium channels. To date, however, no drugs exist that target CRMP2. Recently, the small molecule edonerpic maleate (1 -{3-[2-(1-
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Ion channels as potential redox sensors in lysosomes. Channels (IF 2.311) Pub Date : 2019-10-30 Jie Yu,Junsheng Yang
Lysosomes are central organelles that recycle materials and energy to maintain intracellular homeostasis. Lysosomes are capable of sensing environmental cues such as nutrition to regulate their function accordingly. Whether lysosomes can sense redox signaling, however, was unclear. Here in this review, we summarized recent evidence of lysosomal ion channel as redox sensors for this organelle. We also
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Voltage vs. Ligand I: Structural basis of the intrinsic flexibility of S3 segment and its significance in ion channel activation. Channels (IF 2.311) Pub Date : 2019-10-24 Daniel Balleza,Mario E Rosas,Sergio Romero-Romero
We systematically predict the internal flexibility of the S3 segment, one of the most mobile elements in the voltage-sensor domain. By analyzing the primary amino acid sequences of V-sensor containing proteins, including Hv1, TPC channels and the voltage-sensing phosphatases, we established correlations between the local flexibility and modes of activation for different members of the VGIC superfamily
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