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Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang Huang Wanting Dong Xiaoqian Lin Jinsong Bian Department of Pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Department of Pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

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Toxic medicine used in Traditional Chinese Medicine for cancer treatment: are ion channels involved?

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Journal of Traditional Chinese Medicine 2022年第6期42卷 1019-1022页

作者： LIU Hengrui Biocomma Limited Shenzhen 518000China

Cancer has been one of the most serious public health issues in the world. Traditional medicines are widely used in adjunctive therapies in clinical cancer treatment in many countries. One of the unique traditional medicine usages in tumor treatment is the high-dose application of traditional toxin medicine, including venom or body from toxin animals. Evidence has shown that they are very likely to have direct effects on cancer cells. One of the potential pharmacological effects of traditional toxin medicines is their regulation of ion channels in cancers. Many ion channels are found critical in cancers. This study suggested that ion channels were involved in the effect of traditional toxin medicine on cancers. However, so far, the study of the effect of traditional toxin medicine on ion channels in cancers is relatively lacking. This perspective article urged the study in this field because, given the fact that these traditional toxin traditional medicines have been widely used in cancer treatment, the identification of the effective components and pharmacological targets can improve their clinical application.

关键词： neoplasms ion channels venoms toxin medicine traditional

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Synchronous constructing ion channels and confined space of Co_(3)O_(4) anode for high-performance lithium-ion batteries

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Nano Research 2022年第7期15卷 6192-6199页

作者： Yan Zhou Chao Wang Feiran Chen Tingjuan Wang Yaoyao Ni Hongxia Sun Nan Yu Baoyou Geng College of Chemistry and Materials Science The Key Laboratory of Electrochemical Clean Energy of Anhui Higher Education InstitutesAnhui Provincial Engineering Laboratory for New-Energy Vehicle Battery Energy-Storage MaterialsAnhui Normal UniversityWuhu 241002China Institute of Energy Hefei Comprehensive National Science CenterHefei 230031China

The yolk–shell structure has a unique advantage in lithium-ion batteries applications due to its ability to effectively buffer the volume expansion of the lithiation/delithiation process.However,its development is limited by the low contact point between the core and shell.Herein,we propose a general strategy of simultaneous construction of sufficient reserved space and multicontinuous active channels by pyrolysis of two carbon substrates.A double-shell structure consisting of Co_(3)O_(4) anchored to hollow carbon sphere and external self-supporting zeolitic imidazolate framework(ZIF)layer was constructed by spray pyrolysis and additional carbon coating in-situ growth.In the process of high-temperature calcination,the carbon and nitrogen layers between the shells separate,creating additional space,while the Co_(3)O_(4) particles between the shells remain are still in close contact to form continuous and fast electron conduction channels,which can realize better charge transfer.Due to the synergy of these design principles,the material has ultra-high initial discharge capacities of 2,183.1 mAh·g^(−1) at 0.2 A·g^(−1) with capacity of 1,121.36 mAh·g^(−1) after 250 cycles,the long-term capacities retention rate is about 92.4%after 700 cycles at 1 A·g^(−1).This unique channel-type double-shell structure fights a way out to prepare novel electrode materials with high performance.

关键词： double-shell structure ion channels confined space lithium-ion batteries Co_(3)O_(4)

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Do tensile and shear forces exerted on cells influence mechanotransduction through stored energy considerations?

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BIOCELL 2024年第4期48卷 525-540页

作者： FREDERICK H.SILVER TANMAY DESHMUKH Department of Pathology and Laboratory Medicine Robert Wood Johnson Medical SchoolRutgersThe State University of New JerseyPiscatawayNJ 08854USA OptoVibronex LLC.Ben Franklin Tech PartnersBethlehemPA 18015USA

All tissues in the body are subjected externally to gravity and internally by collagenﬁbril and cellular retractive forces that create stress and energy equilibrium required for homeostasis.Mechanotransduction involves mechanical work(force through a distance)and energy storage as kinetic and potential energy.This leads to changes in cell mitosis or apoptosis and the synthesis or loss of tissue components.It involves the application of energy directly to cells through integrin-mediated processes,cell-cell connections,stretching of the cell cytoplasm,and activation of the cell nucleus via yes-associated protein(YAP)and transcriptional coactivator with PDZ-motif(TAZ).These processes involve numerous complexes,intermediate molecules,and multiple pathways.Several pathways have been identiﬁed from research studies on vertebrate cell culture and from studies in invertebrates.These pathways involve mechanosensors and other molecules that activate the pathways.This review discusses the mitogen-activated protein kinase(MAPK)family,Hippo,Hedgehog,and Wingless-related integration site(WNT)/βcatenin signaling pathways.The mediators covered includeβcatenin,ion channels,growth factors,hormone receptors,members of the Ras superfamily,and components of the linker of nucleoskeleton and cytoskeleton(LINC)complex.However,the interrelationship among the different pathways remains to be clariﬁed.Integrin-mediated mechanotransduction involves direct tensile loading and energy applied to the cell membrane via collagenﬁbril stretching.This energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/βcatenin pathway.These alterations induce changes in intracellular events in the cytoskeleton and nuclear skeleton caused by the release of YAP and TAZ.These coactivators then penetrate through the nuclear pores and inﬂuence nuclear cell function.Alteration in the balance of forces and energy applied to cells and tissues is hypothesized to shift the cell-extracellular matrix mechanical equilibri

关键词： MAPK family Hippo Hedgehog WNT pathway βcatenin ion channels Growth factor receptors Hormone receptors Ras superfamily LINC complex Collagen Cadherins

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ion channels in Plant Bioenergetic Organelles, Chloroplasts and Mitochondria： From Molecular Identification to Function

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Molecular Plant 2016年第3期9卷 371-395页

作者： Luca Carraretto Enrico Teardo Vanessa Checchetto Giovanni Finazzi Nobuyuki Uozumi Ildiko Szabo Department of Biology University of Padova Padova 35121 Italy CNR Institute of Neuroscience University of Padova Padova 35121 Italy UMR 5168 Laboratoire de Physiologie Cellulaire Vegetale (LPCV) CNRS/UJF / INRA / CEA Institut de Recherches en Technologies et Sciences pour le Vivant (iRTSV) CEA Grenoble 38054 Grenoble France Department of Siomolecular Engineering Graduate Schoo~ of Engineering Tohoku University Aobayama 6-6-07 Sendai 980-8579 Japan

Recent technical advances in electrophysiological measurements, organelle-targeted fluorescence imaging, and organelle proteomics have pushed the research of ion transport a step forward in the case of the plant bioenergetic organelles, chloroplasts and mitochondria, leading to the molecular identification and functional characterization of several ion transport systems in recent years. Here we focus on channels that mediate relatively high-rate ion and water flux and summarize the current knowledge in this field, focusing on targeting mechanisms, proteomics, electrophysiology, and physiological function. In addition, since chloroplasts evolved from a cyanobacterial ancestor, we give an overview of the information available about cyanobacterial ion channels and discuss the evolutionary origin of chloroplast channels. The recent molecular identification of some of these ion channels allowed their physiological functions to be studied using genetically modified Arabidopsis plants and cyanobacteria. The view is emerging that alteration of chloroplast and mitochondrial ion homeostasis leads to organelle dysfunction, which in turn significantly affects the energy metabolism of the whole organism. Clear-cut identification of genes encoding for chan- nels in these organelles, however, remains a major challenge in this rapidly developing field. Multiple stra- tegies including bioinformatics, cell biology, electrophysiology, use of organelle-targeted ion-sensitive probes, genetics, and identification of signals eliciting specific ion fluxes across organelle membranes should provide a better understanding of the physiological role of organellar channels and their contribution to signaling pathways in plants in the future.

关键词： ion channels chloroplasts mitochondria cyanobacteria endosymbiosis plant physiology

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The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels

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Chinese Medical Journal 2011年第19期124卷 3105-3111页

作者： WANG Rong-rong LI Ning ZHANG Yin-hui RAN Yu-qin PU Jie-lin Pathology and Physiology Research Center Cardiovascular Institute and Fu Wai Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100037 China

Background Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.Methods Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current （/Ca-L）,inward rectifier potassium current （/K1）, and transient outward potassium current （/to1） were studied in rat ventricular myocytes and sodium current （/Na）, slow delayed rectifier current （/Ks）, and HERG current （/Kr） were investigated in transfected human embryonic kidney 293 cells.Results One hundred μmol/L paeoniflorin reduced the peak /ca-L by 40.29% at the test potential of ±10 mV （from （-9.78±0.52） pA/pF to （-5.84±0.89） pA/pF, n=5, P=0.028）. The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were （-11.22±0.27） mV vs. （-5.95±0.84） mV （n=5,P=0.007）, respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred μmol/L paeoniflorin completely inhibited the peak /Na and the effect was reversible. Moreover,paeoniflorin inhibited the /K1 by 30.13% at the test potential of -100 mV （from （-25.26±8.21） pA/pF to （-17.65±6.52）pA/pF, n=6, F=0.015） without effects on the reversal potential and the rectification property. By contrast, 100 μmol/L paeoniflorin had no effects on/to1, /Ks or /Kr channels.Conclusions The study demonstrated that paeoniflorin blocked /Ca-L, /Na, and /Kf without affecting /to1, /Ks, or /Kr. The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.

关键词： ion channels Chinese herbs antiarrhythmic drugs paeoniflorin

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Effects of Chinese herbs on multiple ion channels in isolated ventricular myocytes

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Chinese Medical Journal 2007年第12期120卷 1068-1074页

作者： LI Ning MA Ke-juan WU Xiang-feng SUN Qi ZHANG Yi-hui PU Jie-lin Center for Arrhythmia Diagnosis and Treatment Fuwai Cardiovascular Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Research Center for Pathology and Physiology Fuwai Cardiovascular Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Research Institute for Medicine Hebei Medical University Shijiazhuang 050035 China

Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.

关键词： ion channels patch clamp antiarrhythmic drugs Shensong Yangxin capsule

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Differences of promethazine and terfenadine on ion channels in guinea pig ventricular myocytes

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Chinese Medical Journal 2006年第11期119卷 944-947页

作者： LI Xue-wen NIU Shuan-cheng ZHANG Xuan-ping Lü Ji-yuan BAI Feng ZHANG Ling WU Bo-wei First Hospital Shanxi Medical University Taiyuan 030001China Department of Pharmacology Shanxi Medical University Taiyuan 030001China Department of Physiology Shanxi Medical University Taiyuan030001China

Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes （TdP） like ventricular arrhythmia.^3 This may be due to the blockage on rectifier postassium current （Ik） of terfenadine, resulting in the prolongation of the action potential duration （APD） and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.^4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the lk and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.

关键词： promethazine terfenadine ion channels ventricular myocytes H1 receptor

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ion channels in liver diseases and hepatocellular carcinoma: potential tools for diagnosis, prognosis, and therapy

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Hepatoma Research 2020年第4期6卷 1-16页

作者： María de Guadalupe Chávez-López Andrea Cruz-Díaz Karla Nicol Tlapalcoyoa-Apanco Julio IsaelPérez-Carreón Javier Camacho Department of Pharmacology Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico City 07360Mexico Escuela de Ciencias de la Salud Universidad del Valle de MéxicoMexico City 04910Mexico Instituto Nacional de Medicina Genómica Mexico City 14610Mexico

Cancer is a major cause of death worldwide.Hepatocellular carcinoma(HCC)is one of the malignancies with the highest mortality-to-incidence ratio(>0.9),and in some countries this value is up to 1.Unfortunately,many patients are diagnosed at advanced stages of the disease.Therefore,HCC early markers,as well as novel therapeutic approaches,are urgently needed.HCC is the main type of liver cancer and it is associated with different factors including alcohol use,viral infections,and fatty liver disease.A significant percentage of HCC patients previously had liver cirrhosis.Several ion channels have been proposed as novel potential markers and therapeutic targets for diverse cancers including HCC.Here,we review most of the findings associating ion channel expression with HCC and its etiological factors,as well as some possible pro-tumorigenic mechanisms of action for ion channels in HCC.Novel therapies for HCC treatment and prevention are also discussed.ion channel targeting offers a plethora of opportunities for HCC prevention,early diagnosis,and therapy that may help to reduce the extremely high mortality-to-incidence ratio of this malignancy.

关键词： ion channels hepatocellular carcinoma hepatitis virus cirrhosis liver disease alcohol

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VGIchan:Prediction and Classification of Voltage-Gated ion channels

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Genomics, Proteomics & Bioinformatics 2006年第4期4卷 253-258页

作者： Sudipto Saha Jyoti Zack Balvinder Singh G.P.S.Raghava Institute of Microbial Technology Chandigarh 160036India.

This study describes methods for predicting and classifying voltage-gated ion channels. Firstly, a standard support vector machine （SVM） method was developed for predicting ion channels by using amino acid composition and dipeptide composition, with an accuracy of 82.89% and 85.56%, respectively. The accuracy of this SVM method was improved from 85.56% to 89.11% when combined with PSIBLAST similarity search. Then we developed an SVM method for classifying ion channels （potassium, sodium, calcium, and chloride） by using dipeptide composition and achieved an overall accuracy of 96.89%. We further achieved a classification accuracy of 97.78% by using a hybrid method that combines dipeptidebased SVM and hidden Markov model methods. A web server VGIchan has been developed for predicting and classifying voltage-gated ion channels using the above approaches. VGIchan is freely available at www.***.res.in/raghava/vgichan/.

关键词： ion channels prediction VGIchan SVM HMM

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