Clancy2001_Kchannel

  public model
Short description

This model is according to the paper Cellular consequences of HEGR mutations in the long QT syndrome: precursors to sudden cardiac death. The author used Markovian model of cardiac Ikr in the paper. Figure4B in the paper has been reproduced using CellDesigner3.5.1. The cell is depolarized to the indicated test potential for 250ms (from 50ms to 300ms) from a holding potential of -40mV and then repolarized to -40mV. Change the value for vtest from -30,-20,-10,0,10,20,30,40 for each simulation in order to produce the different cureve in the paper.


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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V1)
Related Publication
  • Cellular consequences of HERG mutations in the long QT syndrome: precursors to sudden cardiac death.
  • Clancy CE, Rudy Y
  • Cardiovascular research , 5/ 2001 , Volume 50 , pages: 301-313
  • Cardiac Bioelectricity Research and Training Center, Department of Physiology and Biophysics, 509 Wickenden Building, Case Western Reserve University, Cleveland, Ohio 44106-7207, USA.
  • A variety of mutations in HERG, the major subunit of the rapidly activating component of the cardiac delayed rectifier I(Kr), have been found to underlie the congenital Long-QT syndrome, LQT2. LQT2 may give rise to severe arrhythmogenic phenotypes leading to sudden cardiac death.We attempt to elucidate the mechanisms by which heterogeneous LQT2 genotypes can lead to prolongation of the action potential duration (APD) and consequently the QT interval on the ECG.We develop Markovian models of wild-type (WT) and mutant I(Kr) channels and incorporate these models into a comprehensive model of the cardiac ventricular cell.Using this virtual transgenic cell model, we describe the effects of HERG mutations on the cardiac ventricular action potential (AP) and provide insight into the mechanism by which each defect results in a net loss of repolarizing current and prolongation of APD.This study demonstrates which mutations can prolong APD sufficiently to generate early afterdepolarizations (EADs), which may trigger life-threatening arrhythmias. The severity of the phenotype is shown to depend on the specific kinetic changes and how they affect I(Kr) during the time course of the action potential. Clarifying how defects in HERG can lead to impaired cellular electrophysiology can improve our understanding of the link between channel structure and cellular function.
Contributors
Enuo He

Metadata information

is
BioModels Database MODEL2898180293
BioModels Database BIOMD0000000121
isDescribedBy
PubMed 11334834
isDerivedFrom
PubMed 10448858
PubMed 7514509
PubMed 7788872
PubMed 10318671
hasTaxon
Taxonomy Cavia porcellus
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
isHomologTo
OMIM 152427
hasVersion
Human Disease Ontology Andersen-Tawil syndrome
Curation status
Curated
Original model(s)
http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=58172
  • Model originally submitted by : Enuo He
  • Submitted: Jul 5, 2007 9:14:39 AM
  • Last Modified: Apr 27, 2017 7:37:54 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Apr 27, 2017 7:37:54 PM
    • Submitted by: Enuo He
    • With comment: Current version of Clancy2001_Kchannel
  • Version: 1 public model Download this version
    • Submitted on: Jul 5, 2007 9:14:39 AM
    • Submitted by: Enuo He
    • With comment: Original import of Clancy2001_Kchannel
Curator's comment:
(added: 26 Jun 2007, 23:52:30, updated: 26 Jun 2007, 23:52:30)
Figure4B has been reproduced by Celldesigner 3.5.1