Cardiac conduction

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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 Tanya
9:50am Overview of neurobiology describing processes involved in transmitting signal from pacemaker to cardiomyocyte [1] Andy
10:05am Overview of GO signaling guidelines (focus on neurobiology relevant ontology) Becky
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 Amaretto 116 Tottenham Court Road
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 Paola
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


--Questions for experts based on Day 1 discussions and ontology development

1. Do we need to His-Purkinje cell to His-Purkinje cell signalling to capture Bundle of His to Purkinje fiber signalling?

2.Is it the same cell in the Bundle of His that also forms the Purkinje fibers, or are these made of different cells?

3.Which ions are flowing through the gap junctions?

4.Do we need to split all cardiac conduction terms into rate and strength terms?

5.Beta adrenergic signaling, which node is this active in? (Term created may need to be changed; we currently have this as SA node CMC to atrial CMC.)


-- Questions for GO editors and annotators:

1. Can annots to mbe repol (and children) be transferred to reg of mbe repol inv in contraction (and children)?

Attendees

Name Organization
Andy Tinker University College London
Paul Riley Institute of Child Health (unable to attend)
Ross Breckenridge University College London (Friday only)
Pier Lambiase University College London Hospital
Perry Elliot University College London Hospital (Friday only)
Lucie Clapp University College London (Thursday until 2:45pm only)
Ruth Lovering BHF-UCL
Varsha Khodiyar BHF-UCL
David Hill The Jackson Laboratory
Susan Tweedie FlyBase, University of Cambridge
Rebecca Foulger GO editorial office, EBI
Paola Roncaglia GO editorial office, EBI
Tanya Berardini TAIR, Carnegie Institute for Science
Doug Howe Zfin, Remote attendance
Stan Laulederkind RGD

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 (exists, GO:0055117)
    • regulation of heart rate (exists, GO:0002027)
    • strength of heart contraction (heart contraction exists, GO:0060047, regulation terms as well)
    • blood pressure (regulation of blood pressure exists, GO:0008217, ROBQ&)
    • sensing (?)
    • systemic signaling (?)
    • hormone signaling (note forth coming development of this domain, hormone-mediated signaling pathway exists, GO:0009755)
    • action potential (regulation of action potential exists, GO:0001508, RoBQ)
    • long synaptic potential (?)
    • synaptic plasticity (regulation of synaptic plasticity exists, GO:0048167, RoBQ)
    • regulation of membrane potential (exists, GO:0042391)
  • &ROBQ = regulation of biological quality
  • 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.

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
  • 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 [2]

Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca(2+) channel (zebrafish) PMID: 20657579 [3]

The cardiac conduction system. PMID: 21357845 [4]

The Anatomy and Physiology of the Sinoatrial Node—A Contemporary Review PMID: 20946278 [5]

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. [6]

Induction and patterning of the cardiac conduction system. Int J Dev Biol. 2002 Sep;46(6):765-75. Review. PubMed PMID: 12382942. [7]

Development of the cardiac conduction system. Semin Cell Dev Biol. 2007 Feb;18(1):90-100. Epub 2007 Jan 4. Review. PubMed PMID: 17289407. [8]

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. [9]

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. [10] 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 [[11]]

Regulation of skeletal muscle contraction via regulation of the release of sequestered calcium ion [[12]]

Cardiac muscle contraction [[13]]

Regulation of ventricular cardiac muscle repolarization [[14]]

Relaxation of cardiac muscle [[15]]

Heart contraction terms [[16]]

Action potentials and muscle contraction [[17]]

Ontology link between regulation of action potential and membrane depolarization GO terms [[18]]

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 [[19]]

Ontology link between GO:0005267 potassium channel activity and GO:0015079 potassium ion transmembrane transporter activity [[20]]

GO:0005222 synonym [[21]]

Stretch activated cation channel activity [[22]]

Membrane repolarization [[23]]

Muscle and myocyte [[24]]

GO:0003298 physiological muscle hypertrophy additional links [[25]]

Cardiac pacemaker cell [[26]]

GO:0022843 voltage-gated cation channel activity [[27]]

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

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
  • 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

mutations in multiple ion channel genes including KCNQ1, KCNE2, KCNJ2, KCNA5, SUR2A, and SCN5A as well as the gap junction gene GJA5, the nuclear protein NUP155, and the atrial natriuretic peptide precursor NPPA have been associated with atrial fibrillation (AF).

GOC meeting link 2011_UCL_Meeting_Logistics


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