当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES期刊下所有文献 > Pacemaker activity of the human sinoatrial node: an update on the effects of mutations in HCN4 on the hyperpolarization-activated current.

Pacemaker activity of the human sinoatrial node: an update on the effects of mutations in HCN4 on the hyperpolarization-activated current.

Abstract：

:Since 2003, several loss-of-function mutations in the HCN4 gene, which encodes the HCN4 protein, have been associated with sinus node dysfunction. In human sinoatrial node (SAN), HCN4 is the most abundant of the four isoforms of the HCN family. Tetramers of HCN subunits constitute the ion channels that conduct the hyperpolarization-activated "funny" current (If), which plays an important modulating role in SAN pacemaker activity. Voltage-clamp experiments on HCN4 channels expressed in COS-7, CHO and HEK-293 cells, as well as in Xenopus oocytes have revealed changes in the expression and kinetics of mutant channels, but the extent to which especially the kinetic changes would affect If flowing during a human SAN action potential often remains unresolved. In our contribution to the Topical Collection on Human Single Nucleotide Polymorphisms and Disease Diagnostics, we provide an updated review of the mutation-induced changes in the expression and kinetics of HCN4 channels and provide an overview of their effects on If during the time course of a human SAN action potential, as assessed in simulated action potential clamp experiments. Future research may solve apparent inconsistencies between data from clinical studies and data from in vitro and in silico experiments.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Verkerk AO,Wilders R

doi

10.3390/ijms16023071

subject

Has Abstract

pub_date

2015-01-29 00:00:00

pages

3071-94

issue

2

issn

1422-0067

pii

ijms16023071

journal_volume

16

pub_type

杂志文章,评审

相关文献

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES文献大全
  • Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids.

    abstract：:Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms161023849

    authors： Sakuma T,Takenaga M,Kawabe Y,Nakamura T,Kamihira M,Yamamoto T

    更新日期：2015-10-09 00:00:00

  • A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease.

    abstract：:Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible indiv...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章,评审

    doi：10.3390/ijms18071534

    authors： Dongiovanni P,Valenti L

    更新日期：2017-07-16 00:00:00

  • Mapping Quantitative Trait Loci (QTL) for Resistance to Late Blight in Tomato.

    abstract：:Late blight caused by Phytophthora infestans (Montagne, Bary) is a devastating disease of tomato worldwide. There are three known major genes, Ph-1, Ph-2, and Ph-3, conferring resistance to late blight. In addition to these three genes, it is also believed that there are additional factors or quantitative trait loci (...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms18071589

    authors： Panthee DR,Piotrowski A,Ibrahem R

    更新日期：2017-07-22 00:00:00

  • Use of brassica plants in the phytoremediation and biofumigation processes.

    abstract：:In recent decades, serious contamination of soils by heavy metals has been reported. It is therefore a matter of urgency to develop a new and efficient technology for removing contaminants from soil. Another aspect to this problem is that environmental pollution decreases the biological quality of soil, which is why p...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章,评审

    doi：10.3390/ijms12117760

    authors： Szczygłowska M,Piekarska A,Konieczka P,Namieśnik J

    更新日期：2011-01-01 00:00:00

  • InDel Marker Based Estimation of Multi-Gene Allele Contribution and Genetic Variations for Grain Size and Weight in Rice (Oryza sativa L.).

    abstract：:The market success of any rice cultivar is exceedingly dependent on its grain appearance, as well as its grain yield, which define its demand by consumers as well as growers. The present study was undertaken to explore the contribution of nine major genes, qPE9~1, GW2, SLG7, GW5, GS3, GS7, GW8, GS5, and GS2, in regula...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms20194824

    authors： Gull S,Haider Z,Gu H,Raza Khan RA,Miao J,Wenchen T,Uddin S,Ahmad I,Liang G

    更新日期：2019-09-28 00:00:00

  • Dietary Wheat Amylase Trypsin Inhibitors Impact Alzheimer's Disease Pathology in 5xFAD Model Mice.

    abstract：:Wheat amylase trypsin inhibitors (ATIs) represent a common dietary protein component of gluten-containing cereals (wheat, rye, and barley). They act as toll-like receptor 4 ligands, and are largely resistant to intestinal proteases, eliciting a mild inflammatory response within the intestine after oral ingestion. Impo...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21176288

    authors： Dos Santos Guilherme M,Zevallos VF,Pesi A,Stoye NM,Nguyen VTT,Radyushkin K,Schwiertz A,Schmitt U,Schuppan D,Endres K

    更新日期：2020-08-31 00:00:00

  • TRPV3 Channel in Keratinocytes in Scars with Post-Burn Pruritus.

    abstract：:Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of pro...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms18112425

    authors： Park CW,Kim HJ,Choi YW,Chung BY,Woo SY,Song DK,Kim HO

    更新日期：2017-11-15 00:00:00

  • Differential Targeting of Gr-MDSCs, T Cells and Prostate Cancer Cells by Dactolisib and Dasatinib.

    abstract：:Granulocytic myeloid-derived suppressor cells (Gr-MDSCs) promote immune evasion and resistance to immunotherapeutics in a variety of malignancies. Our previous study showed that dual PI3K/mTOR inhibitor Dactolisib impaired the viability and immunosuppressive function of Gr-MDSCs, and significantly synergized with immu...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21072337

    authors： Liu G,Jin Z,Lu X

    更新日期：2020-03-27 00:00:00

  • Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases.

    abstract：:Balanced osteoclast and osteoblast activity is necessary for skeletal health, whereas unbalanced osteoclast activity causes bone loss in many skeletal conditions. A better understanding of pathways that regulate osteoclast differentiation and activity is necessary for the development of new therapies to better manage ...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21031056

    authors： Leightner AC,Mello Guimaraes Meyers C,Evans MD,Mansky KC,Gopalakrishnan R,Jensen ED

    更新日期：2020-02-05 00:00:00

  • Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials.

    abstract：:The ongoing pandemic of coronavirus disease-2019 (COVID-19) is being caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease continues to present significant challenges to the health care systems around the world. This is primarily because of the lack of vaccines to protect against the infe...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章,评审

    doi：10.3390/ijms21155224

    authors： Al-Horani RA,Kar S,Aliter KF

    更新日期：2020-07-23 00:00:00

  • Quantitative Evaluation of the Sarcomere Network of Human hiPSC-Derived Cardiomyocytes Using Single-Molecule Localization Microscopy.

    abstract：:The maturation of iPSC-derived cardiomyocytes is still a critical point for their application in cardiovascular research as well as for their clinical use. Although multiple differentiation protocols have been established, researchers failed to generate fully mature cardiomyocytes in vitro possessing identical phenoty...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21082819

    authors： Lemcke H,Skorska A,Lang CI,Johann L,David R

    更新日期：2020-04-17 00:00:00

  • Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression.

    abstract：:Obesity is a worldwide epidemic problem and correlates to varieties of acute or chronic lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. An increase of leptin, a kind of adipokine, in lean mice plasma has been found to impair immune responses and...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms20051078

    authors： Hsu PS,Lin CM,Chang JF,Wu CS,Sia KC,Lee IT,Huang KY,Lin WN

    更新日期：2019-03-02 00:00:00

  • Nucleotides-Induced Changes in the Mechanical Properties of Living Endothelial Cells and Astrocytes, Analyzed by Atomic Force Microscopy.

    abstract：:Endothelial cells and astrocytes preferentially express metabotropic P2Y nucleotide receptors, which are involved in the maintenance of vascular and neural function. Among these, P2Y1 and P2Y2 receptors appear as main actors, since their stimulation induces intracellular calcium mobilization and activates signaling ca...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms22020624

    authors： Gil-Redondo JC,Iturri J,Ortega F,Pérez-Sen R,Weber A,Miras-Portugal MT,Toca-Herrera JL,Delicado EG

    更新日期：2021-01-10 00:00:00

  • AtPiezo Plays an Important Role in Root Cap Mechanotransduction.

    abstract：:Plants encounter a variety of mechanical stimuli during their growth and development. It is currently believed that mechanosensitive ion channels play an essential role in the initial perception of mechanical force in plants. Over the past decade, the study of Piezo, a mechanosensitive ion channel in animals, has made...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms22010467

    authors： Fang X,Liu B,Shao Q,Huang X,Li J,Luan S,He K

    更新日期：2021-01-05 00:00:00

  • Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability.

    abstract：:Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic c...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章,评审

    doi：10.3390/ijms17060890

    authors： Nielsen AY,Gjerstorff MF

    更新日期：2016-06-06 00:00:00

  • 3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (Tiparp) Knockout Mice.

    abstract：:TCDD-inducible poly-ADP-ribose polymerase (TIPARP) is an aryl hydrocarbon receptor (AHR) target gene that functions as part of a negative feedback loop to repress AHR activity. Tiparp-/- mice exhibit increased sensitivity to the toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including lethal wast...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms20092312

    authors： Cho TE,Bott D,Ahmed S,Hutin D,Gomez A,Tamblyn L,Zhou AC,Watts TH,Grant DM,Matthews J

    更新日期：2019-05-10 00:00:00

  • Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-methylpyrimidine-2, 4-diamine (TH287): A Potential Radiotracer for Measuring and Imaging MTH1.

    abstract：:MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was ...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21228860

    authors： Chen H,Afrin S,Guo Y,Chu W,Benzinger TLS,Rogers BE,Garbow JR,Perlmutter JS,Zhou D,Xu J

    更新日期：2020-11-23 00:00:00

  • Cancer cell cytotoxicities of 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives.

    abstract：:A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a-g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and (1)H nuclear magnetic resonance spectra. Cytotoxicity of t...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms13078071

    authors： Yarim M,Koksal M,Durmaz I,Atalay R

    更新日期：2012-01-01 00:00:00

  • Unique Ca2+-Cycling Protein Abundance and Regulation Sustains Local Ca2+ Releases and Spontaneous Firing of Rabbit Sinoatrial Node Cells.

    abstract：:Spontaneous beating of the heart pacemaker, the sinoatrial node, is generated by sinoatrial node cells (SANC) and caused by gradual change of the membrane potential called diastolic depolarization (DD). Submembrane local Ca2+ releases (LCR) from sarcoplasmic reticulum (SR) occur during late DD and activate an inward N...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章,评审

    doi：10.3390/ijms19082173

    authors： Vinogradova TM,Tagirova Sirenko S,Lakatta EG

    更新日期：2018-07-25 00:00:00

  • Molecular Basis and Clinical Application of Growth-Factor-Independent In Vitro Myeloid Colony Formation in Chronic Myelomonocytic Leukemia.

    abstract：:We have originally reported that colony-forming units granulocyte/macrophage (CFU-GM) formation is an in vitro feature of chronic myelomonocytic leukemia (CMML) and a strong predictor for short survival. Elucidation of the molecular basis underlying this in vitro phenomenon could be helpful to define molecular feature...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21176057

    authors： Geissler K,Jäger E,Barna A,Gurbisz M,Graf T,Graf E,Nösslinger T,Pfeilstöcker M,Machherndl-Spandl S,Stauder R,Zebisch A,Sill H,Öhler L,Kusec R,Hörmann G,Valent P

    更新日期：2020-08-22 00:00:00

  • Proteolipid Protein 2 Overexpression Indicates Aggressive Tumor Behavior and Adverse Prognosis in Human Gliomas.

    abstract：:Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell line...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms19113353

    authors： Chen YH,Hueng DY,Tsai WC

    更新日期：2018-10-26 00:00:00

  • Identification of an AMPK phosphorylation site in Drosophila TSC2 (gigas) that regulate cell growth.

    abstract：:AMP-activated protein kinase (AMPK) is an important metabolic regulator that mediates cellular adaptation to diverse stresses. One of the AMPK substrates, tuberous sclerosis complex 2 (TSC2), was suggested to mediate AMPK-induced silencing of mTOR complex 1 (mTORC1) signaling that is critical for cell growth. However,...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms16047015

    authors： Kim M,Lee JH

    更新日期：2015-03-27 00:00:00

  • Comparison of Fatty Acid Profiles in a Group of Female Patients with Chronic Kidney Diseases (CKD) and Metabolic Syndrome (MetS)⁻Similar Trends of Changes, Different Pathophysiology.

    abstract：:Fatty acid (FA) profiles in the plasma of patients with metabolic syndrome and chronic kidney disease (CKD) seem to be identical despite their different etiology (dietary mistakes vs. cachexia). The aim of this study was to compare both profiles and to highlight the differences that could influence the improvement of ...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms20071719

    authors： Szczuko M,Kaczkan M,Drozd A,Maciejewska D,Palma J,Owczarzak A,Marczuk N,Rutkowski P,Małgorzewicz S

    更新日期：2019-04-06 00:00:00

  • Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients.

    abstract：:It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms17050737

    authors： Tokuda H,Kuroyanagi G,Tsujimoto M,Matsushima-Nishiwaki R,Akamatsu S,Enomoto Y,Iida H,Otsuka T,Ogura S,Iwama T,Kojima K,Kozawa O

    更新日期：2016-05-14 00:00:00

  • Targeting Chemoresistant Tumors: Could TRIM Proteins-p53 Axis Be a Possible Answer?

    abstract：:Chemosensitivity is a crucial feature for all tumours so that they can be successfully treated, but the huge heterogeneity of these diseases, to be intended both inter- and intra-tumour, makes it a hard-to-win battle. Indeed, this genotypic and phenotypic variety, together with the adaptability of tumours, results in ...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章,评审

    doi：10.3390/ijms20071776

    authors： Valletti A,Marzano F,Pesole G,Sbisà E,Tullo A

    更新日期：2019-04-10 00:00:00

  • Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer's Disease.

    abstract：:People with Alzheimer's disease (AD) have significantly higher rates of subclinical and overt epileptiform activity. In animal models, oligomeric Aβ amyloid is able to induce neuronal hyperexcitability even in the early phases of the disease. Such aberrant activity subsequently leads to downstream accumulation of toxi...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章,评审

    doi：10.3390/ijms21239318

    authors： Toniolo S,Sen A,Husain M

    更新日期：2020-12-07 00:00:00

  • APP Maturation and Intracellular Localization Are Controlled by a Specific Inhibitor of 37/67 kDa Laminin-1 Receptor in Neuronal Cells.

    abstract：:Amyloid precursor protein (APP) is processed along both the nonamyloidogenic pathway preventing amyloid beta peptide (Aβ) production and the amyloidogenic pathway, generating Aβ, whose accumulation characterizes Alzheimer's disease. Items of evidence report that the intracellular trafficking plays a key role in the ge...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21051738

    authors： Bhattacharya A,Limone A,Napolitano F,Cerchia C,Parisi S,Minopoli G,Montuori N,Lavecchia A,Sarnataro D

    更新日期：2020-03-04 00:00:00

  • Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice.

    abstract：:In advanced cirrhosis, the TNFα-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities. This st...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms22031233

    authors： Chou YT,Liu TT,Yang UC,Huang CC,Liu CW,Huang SF,Li TH,Liu HM,Lin MW,Yang YY,Lee TY,Huang YH,Hou MC,Lin HC

    更新日期：2021-01-27 00:00:00

  • Multi-Omics Integration Highlights the Role of Ubiquitination in CCl4-Induced Liver Fibrosis.

    abstract：:Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in chronic liver disease. Ubiquitination is a post-translational modification that is crucial for a plethora of physiological processes. Even though the ubiquitin system has been implicated in several human diseases, the role of ...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms21239043

    authors： Mercado-Gómez M,Lopitz-Otsoa F,Azkargorta M,Serrano-Maciá M,Lachiondo-Ortega S,Goikoetxea-Usandizaga N,Rodríguez-Agudo R,Fernández-Ramos D,Bizkarguenaga M,Juan VG,Lectez B,Aloria K,Arizmendi JM,Simon J,Alonso C,Lozano JJ,

    更新日期：2020-11-27 00:00:00

  • Aspirin is Involved in the Cell Cycle Arrest, Apoptosis, Cell Migration, and Invasion of Oral Squamous Cell Carcinoma.

    abstract：:Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. In China, its 5-year survival rate is roughly 50%, owing to acquired chemotherapeutic resistance and metastasis of the disease. Accumulating evidence demonstrates that aspirin (ASA) acts as a preventive or therapeutic agent in multiple ca...

    journal_title：International journal of molecular sciences

    pub_type： 杂志文章

    doi：10.3390/ijms19072029

    authors： Zhang X,Feng H,Li Z,Guo J,Li M

    更新日期：2018-07-12 00:00:00