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.
Authors: Alothaid H, Aldughaim MSK, El Bakkouri K, AlMashhadi S, Al-Qahtani AA 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, comparing HCV with SARS-CoV-2 reveals major similarities between them, ranging from the ion channels that are utilized, to the symptoms t...
Source: Channels - October 25, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Cav2.3 channel function and Zn2+-induced modulation: potential mechanisms and (patho)physiological relevance.
Authors: Neumaier F, Schneider T, Albanna W 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 channels. In the present review, we use these data as a basis to examine the structure, function, and Zn2+-induced modulation of Cav2.3 VGCCs, which mediate native R-type c...
Source: Channels - October 22, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Experimental induction and mathematical modeling of Ca 2+ dynamics in rat round spermatids.
Authors: Saavedra J, Reyes JG, Salinas DG 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+ ] dynamics triggered by blockade of the SERCA transport ATPase with thapsigargin in round rat spermatids, without external Ca2+ and with different extracellular lactate concentrat...
Source: Channels - October 10, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Analysis of Arabidopsis TPK2 and KCO3 reveals structural properties required for K+ channel function.
Authors: Uehara C, Takeda K, Ibuki T, Furuta T, Hoshi N, Tanudjaja E, Uozumi N 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 similarities between TPK2 and KCO3, we evaluated Ca2+ binding to the EF hands in TPK2, and the elements of KCO3 required for K+ channel activ...
Source: Channels - October 7, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Modulation of voltage-gated CaV2.2 Ca2+ channels by newly identified interaction partners.
Authors: Lacinova L, Mallmann RT, Jurkovičová-Tarabová B, Klugbauer N 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, CaV2.2 is an ideal target candidate to search for pharmacological inhibitors but also for novel modulatory interactors. In this review we su...
Source: Channels - October 4, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Modulation of Ca2+-induced Ca2+ release by ubiquitin protein ligase E3 component n-recognin UBR3 and 6 in cardiac myocytes.
Authors: Ma XE, Liu B, Zhao CX 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. In the present study, we found that among the UBR family, single knockdown of UBR3 or UBR6 significantly elevated the amplitude of sarcoplasmic reticulum Ca2+ release without affecting...
Source: Channels - September 30, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Charged pore-lining residues are required for normal channel kinetics in the eukaryotic mechanosensitive ion channel MSL1.
Authors: Schlegel AM, Haswell ES 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 to oxidative stress. Like Escherichia coli MscS, MSL1 has a pore-lining helix that is kinked. However, in MSL1 this kink is comprised of two charged pore-lining residues, R326 and D327. Us...
Source: Channels - September 30, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains.
Authors: Codding SJ, Johnson AA, Trudeau MC Abstract 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 the characteristic gating properties of each type of KCNH channel. The PAS-CNBHD interaction regulates slow closing (deactivation) of hERG channels, the kinetics of a...
Source: Channels - September 16, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Calmodulin binds to the N-terminal domain of the cardiac sodium channel Nav1.5.
In conclusion, we describe the new natural BrS Nav1.5 variant Y87C and present first evidence that calmodulin binds to the Nav1.5 NTD, which seems to be a determinant for the DNE. PMID: 32815768 [PubMed - in process] (Source: Channels)
Source: Channels - August 22, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Loss of Cav1.2 channels impairs hippocampal theta burst stimulation-induced long-term potentiation.
Authors: Sridharan PS, Lu Y, Rice RC, Pieper AA, Rajadhyaksha AM 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 (TBS)-induced LTP in the hippocampus, known to be transcription-independent and dependent on N-methyl D-aspartate receptors (NMDARs) and local prot...
Source: Channels - August 18, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Polymodal roles of TRPC3 channel in the kidney.
Authors: Khayyat NH, Tomilin VN, Zaika O, Pochynyuk O 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 abundantly in the renal vasculature and in epithelial cells, where it is well positioned to mediate signaling and transport functions in response to GPCR-dependent e...
Source: Channels - August 15, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Gap junctions amplify TRPV4 activation-initiated cell injury via modification of intracellular Ca2+ and Ca2+-dependent regulation of TXNIP.
Authors: Zhang X, Mao Z, Huang Y, Zhang Z, Yao J 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 possibility and explored the potential underlying mechanisms. Our results demonstrated that exposure of renal tubular epithelial cells to aminoglycoside G418 led to cell d...
Source: Channels - August 12, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

A low voltage activated Ca2+ current found in a subset of human ventricular myocytes.
In conclusion, ICa-LVA was detected in some HLVMs of a small portion of human hearts that happened to be nonischemic failing hearts. PMID: 32684070 [PubMed - in process] (Source: Channels)
Source: Channels - July 22, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Bibliometric analysis of calcium channel research (2010-2019).
Authors: Shi J, Wang H, Shi S, Yuan G, Jia Q, Shi S, Zhang X, Hu Y 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 publications on calcium channel research in the past decade to explore the hotspots and frontier directions of calcium channel research by bibliometri...
Source: Channels - July 15, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

A bibliometric analysis and review of recent researches on TRPM7.
In this report, a total of 860 publications related to TRPM7 were analyzed. Biophysical Journal ranked top for publishing 31 papers. The United States of America had the largest number of publications (320) with a high citation frequency (11,298) and H-index (58). Chubanov V (38 publications) and Gudermann T (38 citations), who from Ludwig Maximilian University of Munich, were the most productive authors and had the greatest co-citation counts. Our study also combined the bibliometric study with a systematic review on TRPM7, highlighting the four research frontiers of TRPM7. This is the first study that demonstrated the tr...
Source: Channels - July 11, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Sphingosine Kinase 2 Inhibitor ABC294640 Suppresses Neuronal Excitability and Inhibits Multiple Endogenously and Exogenously Expressed Voltage-Gated Ion Channels in Cultured Cells.
Authors: Zhang F, Hu W, Qu L, Cang C Abstract Sphingolipidsregulatemultiplecellularprocesses, including proliferation,autophagy, andapoptosis.Sphingosinekinases,thekeyenzymesinthemetabolismofsphingolipids,areoverexpressedinmanycancers,makingthemimportanttargetsforthedevelopmentof antitumordrugs.ABC294640isaselectivesphingosinekinase2(SK2)inhibitorthatshowsgoodantitumoractivityinvitro. One phaseIclinicalstudyofABC294640reportedthatABC294640causedavarietyofneurologicaldisorders. The mechanismofthesephenomena, however, remainsunclear.Inthepresentstudy,weusedinvitrocellexperimentstotesttheeffectsofABC294640onthenervous...
Source: Channels - July 4, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The Slo3/Lrrc52 complex is sensitive to phosphoinositides.
Authors: Kawai T, Okamura Y 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 been already reported that Slo3 activity is upregulated by PtdIns(4,5)P2 using a heterologous expression system. However, PtdIns(4,5)P2-dependence of Slo3 activity has not been studied in heter...
Source: Channels - June 24, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The effect of MD1 on potassium and L-type calcium current of cardiomyocytes from high-fat diet mice.
Authors: Shuai W, Kong B, Fu H, Jiang X, Huang H 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 of 6 weeks. The potential electrophysiological mechanisms were estimated by whole-cell patch-clamp and molecular analysis. After 20-week HFD feeding, action po...
Source: Channels - June 5, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

A de novo cacna1d missense mutation in a patient with congenital hyperinsulinism, primary hyperaldosteronism and hypotonia.
A DE NOVO CACNA1D MISSENSE MUTATION IN A PATIENT WITH CONGENITAL HYPERINSULINISM, PRIMARY HYPERALDOSTERONISM AND HYPOTONIA. Channels (Austin). 2020 Apr 27;: Authors: De Mingo Alemany MC, Mifsud Grau L, Moreno Macián F, Ferrer Lorente B, León Cariñena S Abstract 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 vo...
Source: Channels - April 29, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The CaMKII phosphorylation site Thr1604 in the CaV1.2 channel is involved in pathological myocardial hypertrophy in rats.
Authors: Li J, Wang S, Zhang J, Liu Y, Zheng X, Ding F, Sun X, Zhao M, Hao L Abstract 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 peptide (AIP) was added as a treatment. Rats in a myocardial hypertrophy development model were subcutaneously injected with ISO f...
Source: Channels - April 16, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The mutation L69P in the PAS domain of the hERG potassium channel results in LQTS by trafficking deficiency.
Authors: Jenewein T, Kanner SA, Bauer D, Hertel B, Colecraft HM, Moroni A, Thiel G, Kauferstein S Abstract 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 are 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 repolarization. In a patient with a clinically diagnosed LQTS we identified the mutation L69P in the N-termi...
Source: Channels - April 9, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Transcriptomic analysis of glycan-processing genes in the dorsal root ganglia of diabetic mice and functional characterization on Cav3.2 channels.
In this study, we aimed to analyze the expression of glycan-processing genes in DRG neurons from a leptin-deficient genetic mouse model of diabetes (db/db). Transcriptomic analysis revealed that several glycan-processing genes encoding for glycosyltransferases and sialic acid-modifying enzymes were upregulated in diabetic conditions. Functional analysis of these enzymes on recombinant Cav3.2 revealed an unexpected loss-of-function of the channel. Collectively, our data indicate that diabetes is associated with an alteration of the glycosylation machinery in DRG neurons. However, individual action of these enzymes when test...
Source: Channels - April 3, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The quest to identify the mechanism underlying adrenergic regulation of cardiac Ca2+ channels.
Authors: Roybal D, Hennessey JA, Marx SO Abstract 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 is readily apparent in heart cells, it has not been possible to reconstitute it in heterologous expression systems. In this review, we describe the efforts of...
Source: Channels - March 21, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells.
Authors: Arbabian A, Iftinca M, Altier C, Singh PP, Isambert H, Coscoy S Abstract 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 conservation of such "ohnolog" genes is theoretically linked to an increased probability of generating phenotypes deleterious ...
Source: Channels - March 20, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The structure and function of TRIP8b, an auxiliary subunit of hyperpolarization-activated cyclic-nucleotide gated channels.
Authors: Han Y, Lyman KA, Foote KM, Chetkovich DM Abstract 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 facilitate a broad range of subcellular distributions, HCN channels are bound by auxiliary subunits that regulate surface trafficking and channel function. One o...
Source: Channels - March 20, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

T-type channels in neuropathic pain - Villain or victim?
Authors: Weiss N PMID: 32167006 [PubMed - in process] (Source: Channels)
Source: Channels - March 14, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Obtaining transition rates from single-channel data without initial parameter seeding.
Conclusions: SCAIM (Single Channel Analysis in MATLAB) facilitate the deduction of kinetic schemes underlying single-channel data. PMID: 32108549 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - February 29, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Regulation of the cold-sensing TRPM8 channels by phosphoinositides and Gq-coupled receptors.
Authors: Liu L, Rohacs T Abstract 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. We will also summarize knowledge on the role of PI(4,5)P2 in Ca2+ dependent desensitization/adaptation of TRPM8 activity, and recent advances in the structural basis of how this...
Source: Channels - February 28, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Activating Sirt1 by resveratrol suppresses Nav1.7 expression in DRG through miR-182 and alleviates neuropathic pain in rats.
Authors: Jia Q, Dong W, Zhang L, Yang X Abstract 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 pain experimentally. Resveratrol with or without miR-182 antagomir were administered to CCI rats via intrathecal catheter. Behavioral tests including paw withdrawal t...
Source: Channels - February 26, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

PAC proton-activated chloride channel contributes to acid-induced cell death in primary rat cortical neurons.
Authors: Osei-Owusu J, Yang J, Del Carmen Vitery M, Tian M, Qiu Z Abstract 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), encoding the proton-activated chloride (Cl-) channel, whose activity is widely observed in human cell lines. We demonstrated that genetic del...
Source: Channels - February 26, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

TRPV1 inhibits smooth muscle cell phenotype switching in a mouse model of abdominal aortic aneurysm.
In this study, we revealed the expression and the pathogenesis of TRPV1 in a mouse AAA model. The results presented here identify TRPV1 could be a potential therapeutic target for AAA treatment. PMID: 32079471 [PubMed - in process] (Source: Channels)
Source: Channels - February 23, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Flow fluorometry quantification of anion channel VRAC subunit LRRC8A at the membrane of living U937 cells.
Authors: Yurinskaya V, Aksenov N, Moshkov A, Goryachaya T, Shemery A, Vereninov A Abstract 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 number of VRAC channels at the cell membrane is responsible for an increase in chloride permeability of the membrane in two well-k...
Source: Channels - February 22, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

TRAM1 protein may support ER protein import by modulating the phospholipid bilayer near the lateral gate of the Sec61-channel.
Authors: Klein MC, Lerner M, Nguyen D, Pfeffer S, Dudek J, Förster F, Helms V, Lang S, Zimmermann R Abstract 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 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. To identify possible determinants of TRAM1 substrate specificity, we systematically identified TRAM1-de...
Source: Channels - February 6, 2020 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Trafficking mechanisms underlying Nav channel subcellular localization in neurons.
Authors: Solé L, Tamkun MM 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 in Nav channel trafficking, localization and regulation. This review summarizes the different trafficking mechanisms underlying the polarized Nav channel localization in neurons, w...
Source: Channels - December 18, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Bibliometric analysis of potassium channel research.
Authors: Shi J, Shi S, Shi S, Jia Q, Yuan G, Chu Y, Wang H, Hu Y, Cui H PMID: 31842669 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - December 18, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Elementary calcium signaling in arterial smooth muscle.
Authors: Fan G, Cui Y, Gollasch M, Kassmann M Abstract 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 reticulum. In arterial SMCs, Ca2+ sparks activate nearby calcium-dependent potassium channels, cause membrane hyperpolarization and thus decrease the global intrac...
Source: Channels - December 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

PI3K α in cardioprotection: Cytoskeleton, late Na+ current, and mechanism of arrhythmias.
PI3Kα in cardioprotection: Cytoskeleton, late Na+ current, and mechanism of arrhythmias. Channels (Austin). 2019 Dec;13(1):520-532 Authors: Zhabyeyev P, Chen X, Vanhaesebroeck B, Oudit GY Abstract 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 poss...
Source: Channels - December 4, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

A conserved arginine/lysine-based motif promotes ER export of KCNE1 and KCNE2 to regulate KCNQ1 channel activity.
Authors: Hu B, Zeng WP, Li X, Al-Sheikh U, Chen SY, Ding J Abstract 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 of KCNE1 have been reported to account for the pathogenesis of LQT5. However, the molecular mechanisms underlying KCNE forward trafficki...
Source: Channels - November 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Evaluation of edonerpic maleate as a CRMP2 inhibitor for pain relief.
Authors: Moutal A, Shan Z, Miranda VG, François-Moutal L, Madura CL, Khanna M, Khanna R Abstract 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-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), a candidate therapeutic for Alzheimer's disease was reported ...
Source: Channels - November 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Ion channels as potential redox sensors in lysosomes.
Authors: Yu J, Yang J Abstract 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 discussed their roles in lysosomal diseases that features imbalanced redox. PMID: 31662029 [PubMed - in process] (Source: Channels)
Source: Channels - November 1, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Voltage vs. Ligand I: Structural basis of the intrinsic flexibility of S3 segment and its significance in ion channel activation.
Authors: Balleza D, Rosas ME, Romero-Romero S Abstract 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. Taking advantage of the structural information available, we also assessed structural aspects to understand the role played by the flexibility of S3 during the g...
Source: Channels - October 27, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Anterograde trafficking signals in GABAA subunits are required for functional expression.
Authors: Nuwer JL, Fleck MW Abstract Pentameric GABAA receptors are composed from 19 possible subunits. The GABAA β subunit is unique because the β1 and β3 subunits can assemble and traffic to the cell surface as homomers, whereas most of the other subunits, including β2, are heteromers. The intracellular domain (ICD) of the GABAA subunits has been implicated in targeting and clustering GABAA receptors at the plasma membrane. Here, we sought to test whether and how the ICD is involved in functional expression of the β3 subunit. Since θ is the most homologous to β but does not for...
Source: Channels - October 17, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The influence of membrane bilayer thickness on KcsA channel activity.
Authors: Callahan KM, Mondou B, Sasseville L, Schwartz JL, D'Avanzo N Abstract Atomic resolution structures have provided significant insight into the gating and permeation mechanisms of various ion channels, including potassium channels. However, ion channels may also be regulated by numerous factors, including the physiochemical properties of the membrane in which they are embedded. For example, the matching of the bilayer's hydrophobic region to the hydrophobic external surface of the ion channel is thought to minimize the energetic penalty needed to solvate hydrophobic residues or exposed lipid tails. To unders...
Source: Channels - October 15, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced relaxations and nitric oxide production in mesenteric arteries: comparative study using wild-type and TRPC1-/- mice.
This study also suggests that heteromeric TRPV4-TRPC1 channels may form the predominant TRPV4-containing channels in mouse mesenteric artery ECs. Together, our data further implicates CaSR-induced pathways and heteromeric TRPV4/TRPC1 channels in the regulation of vascular tone. PMID: 31603369 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - October 12, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Voltage vs. Ligand II: Structural insights of the intrinsic flexibility in cyclic nucleotide-gated channels.
In this study, we describe in detail the flexibility profile of the voltage-sensor domain (VSD) and the pore domain (PD) concerning the evolution of 6TM ion channels. In particular, we highlight the role of flexibility in the emergence of CNG channels and describe a significant level of sequence similarity between the archetypical VSD and the TolQ proteins. A highly flexible S4-like segment exhibiting Lys instead Arg for these membrane proteins is reported. Sequence analysis indicates that, in addition to this S4-like segment, TolQ proteins also show similarity with specific motifs in S2 and S3 from typical V-sensors. Nota...
Source: Channels - September 27, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

TRPML1 and RAS-driven cancers - exploring a link with great therapeutic potential.
Authors: Jung J, Venkatachalam K Abstract Activating mutations in the RAS family of proto-oncogenes represent some of the leading causes of cancer. Unmitigated proliferation of cells harboring oncogenic RAS mutations is accompanied by a massive increase in cellular bioenergetic demands, which offers unique opportunities for therapeutic intervention. To withstand the steep requirements for metabolic intermediates, RAS-driven cancer cells enhance endolysosome and autophagosome biogenesis. By degrading cellular macromolecules into metabolites that can be used by biosynthetic pathways, endolysosomes permit continued pr...
Source: Channels - September 20, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Acid-sensing ion channels mediate the degeneration of intervertebral disc via various pathways-A systematic review.
Authors: Guo Y, Meng Y, Liu H, Wang B, Ding C, Rong X, Yang Y, Hong Y Abstract To elucidate the pathological significance of acid-sensing ion channels (ASICs) in intervertebral disc degeneration (IVDD), the database of Medline, Web of Science, and EmBase were carefully screened. Search terms used in each database varied slightly to optimize results. Data relating to the correlation between ASICs and IVDD was systematically collected and integrated into the review. 11 basic science studies, containing the related information, were finally identified for inclusion. Intervertebral disc degeneration (IVDD) is a common ...
Source: Channels - September 20, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Voltage Gated Sodium Channels in Cancer and Their Potential Mechanisms of Action.
Authors: Angus M, Ruben P Abstract Voltage gated sodium channels (VGSC) are implicated in cancer cell invasion and metastasis. However, the mechanism by which VGSC increase cell invasiveness and probability of metastasis is still unknown. In this review we outline lesser known functions of VGSC outside of action potential propagation, and the current understanding of the effects of VGSC in cancer. Finally, we discuss possible downstream effects of VGSC activation in cancer cells. After extensive review of the literature, the most likely role of VGSC in cancer is in the invadopodia, the leading edge of metastatic ca...
Source: Channels - September 14, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Myrcene and terpene regulation of TRPV1.
Authors: Jansen C, Shimoda LMN, Kawakami JK, Ang L, Bacani AJ, Baker JD, Badowski C, Speck M, Stokes AJ, Small-Howard AL, Turner H Abstract Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the Cannabis component myrcene have been suggested as pain therapeutics, we screened terpenes found in Cannabis for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced c...
Source: Channels - August 28, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Role of the voltage sensor module in Nav domain Ⅳ on fast inactivation in sodium channelopathies: The implication of closed-state inactivation.
Authors: Nakajima T, Kaneko Y, Dharmawan T, Kurabayashi M Abstract The segment 4 (S4) voltage sensor in voltage-gated sodium channels (Navs) have domain-specific functions, and the S4 segment in domain DⅣ (DⅣS4) plays a key role in the activation and fast inactivation processes through the coupling of arginine residues in DⅣS4 with residues of putative gating charge transfer center (pGCTC) in DⅣS1-3. In addition, the first four arginine residues (R1-R4) in Nav DⅣS4 have position-specific functions in the fast inactivation process, and mutations in these residues are associated with diverse phenotypes of N...
Source: Channels - August 1, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research