Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes
Norway

PMID:29097735  

Mammalian γ2 AMPK regulates intrinsic heart rate.

Arash Yavari | Mohamed Bellahcene | Annalisa Bucchi | Syevda Sirenko | Katalin Pinter | Neil Herring | Julia J Jung | Kirill V Tarasov | Emily J Sharpe | Markus Wolfien | Gabor Czibik | Violetta Steeples | Sahar Ghaffari | Chinh Nguyen | Alexander Stockenhuber | Joshua R St Clair | Christian Rimmbach | Yosuke Okamoto | Dongmei Yang | Mingyi Wang | Bruce D Ziman | Jack M Moen | Daniel R Riordon | Christopher Ramirez | Manuel Paina | Joonho Lee | Jing Zhang | Ismayil Ahmet | Michael G Matt | Yelena S Tarasova | Dilair Baban | Natasha Sahgal | Helen Lockstone | Rathi Puliyadi | Joseph de Bono | Owen M Siggs | John Gomes | Hannah Muskett | Mahon L Maguire | Youlia Beglov | Matthew Kelly | Pedro P N Dos Santos | Nicola J Bright | Angela Woods | Katja Gehmlich | Henrik Isackson | Gillian Douglas | David J P Ferguson | Jürgen E Schneider | Andrew Tinker | Olaf Wolkenhauer | Keith M Channon | Richard J Cornall | Eduardo B Sternick | David J Paterson | Charles S Redwood | David Carling | Catherine Proenza | Robert David | Mirko Baruscotti | Dario DiFrancesco | Edward G Lakatta | Hugh Watkins | Houman Ashrafian
Nature communications | 2017

AMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αβγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia). Here, we show that γ2 AMPK activation downregulates fundamental sinoatrial cell pacemaker mechanisms to lower heart rate, including sarcolemmal hyperpolarization-activated current (I f) and ryanodine receptor-derived diastolic local subsarcolemmal Ca2+ release. In contrast, loss of γ2 AMPK induces a reciprocal phenotype of increased heart rate, and prevents the adaptive intrinsic bradycardia of endurance training. Our results reveal that in mammals, for which heart rate is a key determinant of cardiac energy demand, AMPK functions in an organ-specific manner to maintain cardiac energy homeostasis and determines cardiac physiological adaptation to exercise by modulating intrinsic sinoatrial cell behavior.

Pubmed ID: 29097735

Associated grants

  • Agency: British Heart Foundation, United Kingdom
    Id: RG/07/012/24110
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/12/5/29576
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/12/16/29939
  • Agency: British Heart Foundation, United Kingdom
    Id: PG/14/41/30877
  • Agency: British Heart Foundation, United Kingdom
    Id: FS/11/50/29038
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/07/003/23133
  • Agency: Wellcome Trust, United Kingdom
    Id: 086632/Z/08/Z
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL088427
  • Agency: Medical Research Council, United Kingdom
    Id: G0600829
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12010/6
  • Agency: British Heart Foundation, United Kingdom
    Id: FS/15/8/31155
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U120027537
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00008/6
  • Agency: Medical Research Council, United Kingdom
    Id: G0200482
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/17/10/32859
  • Agency: British Heart Foundation, United Kingdom
    Id: FS/12/40/29712

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


GE Healthcare (tool)

RRID:SCR_000004

A commercial antibody supplier and provider of various services.

View all literature mentions

Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

View all literature mentions

Bio-Rad Laboratories (tool)

RRID:SCR_008426

Commercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.

View all literature mentions

Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

View all literature mentions

Vector BioLabs (tool)

RRID:SCR_011010

Biotechnology company focused on developing robust gene delivery products, by using its proprietary technologies. Since 2004, we have worked with over 300 research labs in 20 different countries to provide gene delivery products and services using many viral platforms including recombinant adenoviruses, adeno-associated virus (AAV) and lentivirus.

View all literature mentions

PANTHER (tool)

RRID:SCR_004869

System that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.

View all literature mentions

DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

View all literature mentions

Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

View all literature mentions

Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

View all literature mentions

ClueGO (tool)

RRID:SCR_005748

A Cytoscape plug-in that visualizes the non-redundant biological terms for large clusters of genes in a functionally grouped network. It can be used in combination with GOlorize. The identifiers can be uploaded from a text file or interactively from a network of Cytoscape. The type of identifiers supported can be easily extended by the user. ClueGO performs single cluster analysis and comparison of clusters. From the ontology sources used, the terms are selected by different filter criteria. The related terms which share similar associated genes can be combined to reduce redundancy. The ClueGO network is created with kappa statistics and reflects the relationships between the terms based on the similarity of their associated genes. On the network, the node colour can be switched between functional groups and clusters distribution. ClueGO charts are underlying the specificity and the common aspects of the biological role. The significance of the terms and groups is automatically calculated. ClueGO is easy updatable with the newest files from Gene Ontology and KEGG. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

View all literature mentions

Ingenuity Pathway Analysis (tool)

RRID:SCR_008653

A web-based software application that enables users to analyze, integrate, and understand data derived from gene expression, microRNA, and SNP microarrays, metabolomics, proteomics, and RNA-Seq experiments, and small-scale experiments that generate gene and chemical lists. Users can search for targeted information on genes, proteins, chemicals, and drugs, and build interactive models of experimental systems. IPA allows exploration of molecular, chemical, gene, protein and miRNA interactions, creation of custom molecular pathways, and the ability to view and modify metabolic, signaling, and toxicological canonical pathways. In addition to the networks and pathways that can be created, IPA can provide multiple layering of additional information, such as drugs, disease genes, expression data, cellular functions and processes, or a researchers own genes or chemicals of interest.

View all literature mentions

KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

View all literature mentions

C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions