Difference between revisions of "Cardiac conduction"

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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
  1. 2011 Cardiac conduction workshop Logistics

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 Check terms are applicable across Bilateria Susan
10:00am Overview of neurobiology describing processes involved in transmitting signal from pacemaker to cardiomyocyte Andy?
10:10am Overview of GO description of signal transmission from pacemaker to cardiomyocyte David
10:20am signal transmission from pacemaker to cardiomyocyte ontology development discussion
11am 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
12:30pm Lunch at Ask on Grafton Way. Menu
2:00pm Overview of cardiac muscle contraction, depolarisation and repolarisation and relationship to electrocardiogram
2:15pm Overview of GO description of cardiac muscle contraction, depolarisation and repolarisation David
2:30pm cardiac muscle contraction ontology development discussion
3:45pm Coffee break
4:00pm Round up discussion on cardiac muscle contraction ontology development
4:30pm Are there any areas not covered (other than regulation processes) 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 Complete annotation documentation, decide how specific genes known to be involved in various cardiac conduction processes will be annotated using the new ontology
11am Coffee break
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)


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
  • David and Tanya
    • Set up overview of ontology
  • 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

PMID: 21538814 Screen shot 2011-05-20 at 22.40.36.png

cardiac action potential cartoon

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


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


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?)


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).


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
  • 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.


  • 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.
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