Cardiac conduction
GOC meeting link 2011_UCL_Meeting_Logistics
Venue and date
- South Wing Committee Room, University College London, Thursday 10th and Friday 11th (1/2 day) November 2011
Draft Programme
Thursday 10th November 2011 (room booked 9am-6pm)
9:15am | Coffee and breakfast pastries | ||
9:30am | Welcome and introduction overall aim of workshop | Ruth | |
9:35am | Introduction to GO | David | |
9:50am | Overview of neurobiology describing processes involved in transmitting signal from pacemaker to cardiomyocyte | Andy | |
10:05am | Overview of GO description of signal transmission from pacemaker to cardiomyocyte | David | |
10:20am | signal transmission from pacemaker to cardiomyocyte ontology development discussion | ||
11:00am | Coffee break | ||
11:15am | Continuing signal transmission from pacemaker to cardiomyocyte ontology development discussion | ||
12:10am | Round up discussion on signal transmission from pacemaker to cardiomyocyte ontology development, and use of new terms in annotation | ||
12:30pm | Lunch at Ask on Grafton Way. Menu | ||
2:00pm | Overview of GO description of processes involved in regulation of heart rate | David | |
2:10pm | Processes involved in regulation of heart rate ontology development discussion | ||
3:30pm | Tea break | ||
3:45pm | Continuing processes involved in regulation of heart rate ontology development discussion | ||
4:20pm | Round up discussion on processes involved in regulation of heart rate ontology development, and use of new terms in annotation | ||
4:40pm | Are there any areas not covered (other than cardiac muscle contraction) which need to be included tomorrow | ||
5pm | Close |
Friday 11th November 2011 (room booked 9am to 1pm)
9:15am | Coffee and breakfast pastries | ||
9:30am | Welcome back and questions | Ruth | |
9:35am | Overview of cardiac muscle contraction, depolarisation and repolarisation and relationship to electrocardiogram and channelopathies | Andy | |
9:50am | Overview of GO description of cardiac muscle contraction, depolarisation and repolarisation | David | |
10:00am | Cardiac muscle contraction ontology development discussion | ||
11:00am | Coffee break | ||
11:15am | Continuing cardiac muscle contraction ontology development discussion | ||
12:40pm | Round up discussion on cardiac muscle contraction ontology development, and use of new terms in annotation | ||
1pm | Close |
Items to add to Programme
Please add any items to be added to the programme below
Working group
GO curators and editors: David, Ruth, Doug, Tanya, Becky, Paola, Stan, Susan
Expert scientists:
- Agreed to attend:
- Prof Peter Scambler p.scambler@ich.ucl.ac.uk (if needed)
- Prof Shoumo Bhattacharya shoumo@me.com
- Prof Paul Riley p.riley@ich.ucl.ac.uk
- Dr Ross A Breckenridge r.breckenridge@ucl.ac.uk (available on Thursday, probably not able to attend on Friday)
- Prof Andrew Tinker rmhaant@ucl.ac.uk
- Dr Pier Lambiase pier.lambiase@uclh.nhs.uk Consultant Cardiologist
- Bernard de Bono (virtual physiology)
Attendees
Name | Organization | Vegetarian (Y/N) |
---|---|---|
Ruth Lovering | BHF-UCL | N |
Varsha Khodiyar | BHF-UCL | N |
David Hill | The Jackson Laboratory | N |
Susan Tweedie | FlyBase, University of Cambridge | N |
Rebecca Foulger | GO editorial office, EBI | N |
Paola Roncaglia | GO editorial office, EBI | N |
Tanya Berardini | TAIR, Carnegie Institute for Science | N |
Doug Howe | Zfin | Remote attendance |
Stan Laulederkind | RGD | N |
Minutes GOC Satellite meeting 5:30 - 6:30 Thursday 19th May 2011 LA
- David, Ruth, Doug, Tanya, Becky, Paola, Stan
- Currently only 2 GO terms in this ontology:
- Cardiac conduction
- Atrioventricular node impulse conduction delay
- Missing links/terms
- regulation of cardiac muscle contraction
- regulation of heart rate
- strength of heart contraction
- blood pressure
- sensing
- systemic signaling
- hormone signaling (note forth coming development of this domain)
- action potential
- long synaptic potential
- synaptic plasticity
- regulation of membrane potential
- Ontology for development of the cardiac conduction system pretty much sorted, maybe a few additional cell types to add, but this shouldn't be the scope of this workshop.
- Workshop for ontology for neurological terms on 7th September 2011 - NOTE This has been delayed and might happen the week after the London GOC meeting/cardiac conduction workshop, but it's not sure yet.
- Ideally Paola to attend this meeting (note Paola has a neurobiology background)
Action items
- All:
- Work towards identifying scope of workshop, set by mid July
- Set up table for annotation guide - what genes to annotate to these new GO terms, perhaps capture experimental information here. Eg how to interpret changes in P or QRS intervals associated with specific genes.
- Add figures to wiki to illustrate cardiac conduction processes
- Add useful reviews/papers to wiki
- Ruth:
- Contact experts above (max 5 experts)
- Book rooms
- Ask experts to review blood pressure ontology
- Ask Varsha for her draft ontology
- Doug:
- Look at differences and similarities between zebrafish and mammalian cardiac conduction processes
- My notes on comparative anatomy and functioning of card. cond.
- David and Tanya
- Set up overview of ontology
- Stan
- Review hormone literature/ontology
- Aspects of cardiac conduction affected by hormones
- Paola
- Pacemaker
- Susan
- Look at differences and similarities between Drosophila and mammalian cardiac conduction processes
- Becky
- Look at key signaling pathways that regulate heart rate & cardiac conduction.
Useful papers
The emerging genetic landscape underlying cardiac conduction system function PMID: 21538814 [1]
Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca(2+) channel (zebrafish) PMID: 20657579 [2]
The cardiac conduction system. PMID: 21357845 [3]
The Anatomy and Physiology of the Sinoatrial Node—A Contemporary Review PMID: 20946278 [4]
Genetic and physiologic dissection of the vertebrate cardiac conduction system. PLoS Biol. 2008 May 13;6(5):e109. PubMed PMID: 18479184; PubMed Central PMCID: PMC2430899. [5]
Induction and patterning of the cardiac conduction system. Int J Dev Biol. 2002 Sep;46(6):765-75. Review. PubMed PMID: 12382942. [6]
Development of the cardiac conduction system. Semin Cell Dev Biol. 2007 Feb;18(1):90-100. Epub 2007 Jan 4. Review. PubMed PMID: 17289407. [7]
Neuregulin-1 promotes formation of the murine cardiac conduction system. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10464-9. Epub 2002 Jul 29. PubMed PMID: 12149465; PubMed Central PMCID: PMC124940. [8]
The heart and heart conducting system in the kingdom of animals: A comparative approach to its evolution. Exp Clin Cardiol. 2007 Fall;12(3):113-8. PubMed PMID: 18650991; PubMed Central PMCID: PMC2323757. [9] GREAT COVERAGE OF COMPARATIVE ANATOMY AND FUNCTION OF CARDIAC CONDUCTION SYSTEMS
Useful figures
Relevant Source Forge Requests
Cardiac conduction [[10]]
Regulation of skeletal muscle contraction via regulation of the release of sequestered calcium ion [[11]]
Cardiac muscle contraction [[12]]
Regulation of ventricular cardiac muscle repolarization [[13]]
Relaxation of cardiac muscle [[14]]
Heart contraction terms [[15]]
Action potentials and muscle contraction [[16]]
Ontology link between regulation of action potential and membrane depolarization GO terms [[17]]
Ontology link between GO:0005248 voltage-gated sodium channel activity and GO:0090072 positive regulation of sodium ion transport via voltage-gated sodium channel activity [[18]]
Ontology link between GO:0005267 potassium channel activity and GO:0015079 potassium ion transmembrane transporter activity [[19]]
Ontology discussion documents
Varsha's original ontology suggestions File:HeartConductionDraftOntology2009.pdf
Varsha's notes on discussion of ontology with Andy Tinker File:HeartConductionOntologyDiscussion.pdf
Ontology queries
SCN5A
encodes for the major cardiac voltage-gated Na+ channel (PMID:14500339[1]) which is associated with human arrhythmic syndromes (PMID:21895525[2]). Which of the following process terms should it be annotated to
- cardiac muscle contraction (regulation term better)
- positive regulation of cardiac muscle contraction
- positive regulation of heart rate, or just regulation of heart rate?
- New term: sodium ion import is a child to sodium ion transmembrane transport
- New term: action potential propagation via sodium ion import is a child to sodium ion transmembrane transport
- cardiac conduction
- regulation of atrial cardiomyocyte membrane repolarization (or new parent atrial cardiomyocyte membrane repolarization)
- regulation of ventricular cardiomyocyte membrane repolarization (or new parent term: ventricular cardiomyocyte membrane repolarization)
- positive regulation of action potential or new term initiation of action potential, or is 'action potential' covered by membrane depolarization
- in line with regulation of skeletal muscle contraction via membrane action potential new term regulation of cardiomyocyte contraction via membrane action potential
- membrane depolarization
- regulation of ventricular cardiomyocyte membrane depolarization
- regulation of atrial cardiomyocyte membrane depolarization
- New GO term cardiomyocyte/heart refractory period
- New GO term propagation of the action potential, or is this covered by membrane depolarization
- New GO term(s) to describe 'plateau phase of the cardiac action potential', 'persistent or late inward current (INaL)', 'duration of the cardiac action potential', 'current decay'.
- mutation in SCN5A leads to a prologation of Q-T interval, need some parent terms such as 'regulation of cardiomyocyte membrane depolarization', 'regulation of cardiomyocyte membrane repolarization' 'regulation of cardiomyocyte membrane potential' to capture information about changes in the ECG measurements.
- At present the GO term GO:0008015 'blood circulation' is only linked to SNC5A via 'regulation' terms, should SNC5A be transitively associated with 'blood circulation', and if so how?
- PMID:21051419 describes SCN5A as responsible for the early fast depolarization upstroke of the cardiac action potential, would this be covered by new GO term ventricular cardiomyocyte membrane repolarization.
SCN1B
Sodium channel β1- and β2-subunits (SCN1B, SCN2B) also associated with cardiac conduction associated diseases (PMID:19808477[3]). From this paper: Functions attributed to β-subunits include an increase in sodium channel expression at the cell surface, modulation of channel gating and voltage dependence, and a role in cell adhesion and recruitment of cytosolic proteins such as ankyrin G.
- would it be appropriate to annotate with GO:0090314 positive regulation of sodium channel targeting to membrane, and to use Column 16 to identify SCN5A as the target, or to request new GO term positive regulation of protein targeting to plasma membrane
- GO:0090072 positive regulation of sodium ion transport via voltage-gated sodium channel activity covers 'modulation of channel gating', but does it also capture 'modulation of voltage dependence'
- GO:0070201 regulation of establishment of protein localization? or
- New GO term: regulation of establishment of sodium channel localization in plasma membrane is_a child of GO:0090003 regulation of establishment of protein localization in plasma membrane
- described as auxiliary function-modifying β-subunits, so should they be annotated (as they are) to the GO function term GO:0005248 voltage-gated sodium channel activity?
- Mutation in SCN1B associated with atrial fibrillation (AF), if this is associated with an absence of P waves can this be annotated as GO:0060371 regulation of atrial cardiomyocyte membrane depolarization? Although it looks like the ECGs were mostly normal (saddle-back type ST-segment elevation in some patients).
PMID:14622265 cloning a splicing variant of SCN1B, are sufficient GO terms available to capture these neurological statements? Functional studies in oocytes demonstrate that the human β1B subunit increases the ionic current when coexpressed with the tetrodotoxin sensitive channel, NaV1.2, without significantly changing voltage dependent kinetics and steady-state properties. GO:0003254 regulation of membrane depolarization, can GO provide a more specific term?
Splicing variant 1B only regulation of NaV1.2 was to increase the sodium current density.
- New GO term: positive regulation of sodium current density (what is density?)
SCN3B
PMID:19796257 K/O mouse
- GO:0010460 positive regulation of heart rate (ECG confirmes K/O slower Heart rate)
- GO:0060371 regulation of atrial cardiomyocyte membrane depolarization (K/O has longer P wave duration) do we need positive and negative terms?
- GO:0061338 atrioventricular node impulse conduction delay (K/O showed evidence of A-V heart block; atrial deflections, irregularly timed; ventricular deflections, asynchronous and at irregular intervals)
- New GO term sinoatrial node conduction? (K/O missing atrial deflections in the BEG recordings: suggestive of sinus node exit block)
PMID: 21051419: 3 non-synonymous SCN3B mutations associated with Atrial fibrillation (AF)
- GO:0090072 positive regulation of sodium ion transport via voltage-gated sodium channel activity to capture mutations in SCN3B led to a decrease in peak current density and/or steady-state inactivation (transient transfection of CHO cells).
KCNQ1 & KCNE1
PMID:8900283 cotransfection into CHO cells
- GO:0005251 delayed rectifier potassium channel activity, (associated with KCNQ1) this term should have additional GO parents see SourceForge item.
- KCNQ1 & KCNE1 coassemble to form I(Ks) channels, and dysfunction of I(Ks) channels and mutations in KCNQ1 cause Long QT interval syndrome.
- Can we have a GO term which links the channel activity with cardiomyocyte membrane depolorization? And link cardiomyocyte membrane depolorization with regulation of cardiac muscle contraction?
- See SCN5A suggestion: new term regulation of cardiomyocyte contraction via membrane action potential
- Can we have a GO term which links the channel activity with cardiomyocyte membrane depolorization? And link cardiomyocyte membrane depolorization with regulation of cardiac muscle contraction?
- Also need new GO term similar to GO:0090072 (sodium channel term) positive regulation of potassium ion transport via voltage-gated potassium channel activity
PMID: 8528244 mutations in KCNQ1 lead to cardiac arrhythmias
- Authors state: prolongation of the QT interval is an indication of abnormal cardiac repolarization. Can a Long QT interval be caused by abnormal depolarization?
- new GO term: cardiomyocyte membrane repolarization, as atrial or ventricular not identified
- added GO:0060306 regulation of membrane repolarization based on this mutation, but cardiomyocyte membrane repolarization would be a better annotation.
Other
- what does 'density' in the phrase 'sodium channel current (INa) density' mean?
mutations in multiple ion channel genes including KCNQ1, KCNE2, KCNJ2, KCNA5, SUR2A, and SCN5A as well as the gap junction gene GJA5 and the nuclear protein NUP155 have been associated with AF.