Fink2008_VentricularActionPotential
Ontology highlight
ABSTRACT:
SUBMITTER: 
Camille Laibe
PROVIDER: MODEL1006230009 | BioModels | 2005-01-01
REPOSITORIES: BioModels
Publications
Contributions of HERG K+ current to repolarization of the human ventricular action potential.
Fink Martin M Noble Denis D Virag Laszlo L Varro Andras A Giles Wayne R WR
Progress in biophysics and molecular biology 20070809 1-3
Action potential repolarization in the mammalian heart is governed by interactions of a number of time- and voltage-dependent channel-mediated currents, as well as contributions from the Na+/Ca2+ exchanger and the Na+/K+ pump. Recent work has shown that one of the K+ currents (HERG) which contributes to repolarization in mammalian ventricle is a locus at which a number of point mutations can have significant functional consequences. In addition, the remarkable sensitivity of this K+ channel isof ...[more]
Similar Datasets
Project description:This a model from the article:
Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium.
Maleckar MM, Greenstein JL, Trayanova NA, Giles WR. Prog Biophys Mol Biol.
2008; 98(2-3):161-70 19186188
,
Abstract:
In the mammalian heart, myocytes and fibroblasts can communicate via gap junction, or connexin-mediated current flow. Some of the effects of this electroto
nic coupling on the action potential waveform of the human ventricular myocyte have been analyzed in detail. The present study employs a recently developed
mathematical model of the human atrial myocyte to investigate the consequences of this heterogeneous cell-cell interaction on the action potential of the
human atrium. Two independent physiological processes which alter the physiology of the human atrium have been studied. i) The effects of the autonomic tra
nsmitter acetylcholine on the atrial action potential have been investigated by inclusion of a time-independent, acetylcholine-activated K(+) current in th
is mathematical model of the atrial myocyte. ii) A non-selective cation current which is activated by natriuretic peptides has been incorporated into a pre
viously published mathematical model of the cardiac fibroblast. These results identify subtle effects of acetylcholine, which arise from the nonlinear inte
ractions between ionic currents in the human atrial myocyte. They also illustrate marked alterations in the action potential waveform arising from fibrobla
st-myocyte source-sink principles when the natriuretic peptide-mediated cation conductance is activated. Additional calculations also illustrate the effect
s of simultaneous activation of both of these cell-type specific conductances within the atrial myocardium. This study provides a basis for beginning to as
sess the utility of mathematical modeling in understanding detailed cell-cell interactions within the complex paracrine environment of the human atrial myo
cardium.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Maleckar MM, Greenstein JL, Trayanova NA, Giles WR. (2009) - version01
The original CellML model was created by:
Fink, Martin,
martin.fink@dpag.ox.ac.uk
The University of Oxford
Department of Physiology, Anatomy & Genetics
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
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.
2005-01-01 | MODEL9810152478 | BioModels
Project description:This a model from the article:
A model of the action potential and underlying membrane currents in a rabbit
atrial cell.
Lindblad DS, Murphey CR, Clark JW, Giles WR. Am J Physiol
1996 Oct;271(4 Pt 2):H1666-96 8897964
,
Abstract:
We have developed a mathematical model of the rabbit atrial myocyte and have
used it in an examination of the ionic basis of the atrial action potential.
Available biophysical data have been incorporated into the model to quantify the
specific ultrastructural morphology, intracellular ion buffering, and time- and
voltage-dependent currents and transport mechanisms of the rabbit atrial cell.
When possible, mathematical expressions describing ionic currents identified in
rabbit atrium are based on whole cell voltage-clamp data from enzymatically
isolated rabbit atrial myocytes. This membrane model is coupled to equations
describing Na+, K+, and Ca2+ homeostasis, including the uptake and release of
Ca2+ by the sarcoplasmic reticulum and Ca2+ buffering. The resulting formulation
can accurately simulate the whole cell voltage-clamp data on which it is based
and provides fits to a family of rabbit atrial cell action potentials obtained
at 35 degrees C over a range of stimulus rates (0.2-3.0 Hz). The model is
utilized to provide a qualitative prediction of the intracellular Ca2+
concentration transient during the action potential and to illustrate the
interactions between membrane currents that underlie repolarization in the
rabbit atrial myocyte.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Lindblad DS, Murphey CR, Clark JW, Giles WR. (1996) - version=1.0
The original CellML model was created by:
Penny Noble
penny.noble@dpag.ox.ac.uk
The University of Oxford
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.
.
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.
2005-01-01 | MODEL1006230015 | BioModels
Project description:This a model from the article:
Simulation study of cellular electric properties in heart failure
Priebe L, Beuckelmann DJ. Circ Res.
1998; 82(11):1206-23 9633920
,
Abstract:
Patients with severe heart failure are at high risk of sudden cardiac death. In the majority of these patients, sudden cardiac death is thought to be due to ventricular tachyarrhythmias. Alterations of the electric properties of single myocytes in heart failure may favor the occurrence of ventricular arrhythmias in these patients by inducing early or delayed afterdepolarizations. Mathematical models of the cellular action potential and its underlying ionic currents could help to elucidate possible arrhythmogenic mechanisms on a cellular level. In the present study, selected ionic currents based on human data are incorporated into a model of the ventricular action potential for the purpose of studying the cellular electrophysiological consequences of heart failure. Ionic currents that are not yet sufficiently characterized in human ventricular myocytes are adopted from the action potential model developed by Luo and Rudy (LR model). The main results obtained from this model are as follows: The action potential in ventricular myocytes from failing hearts is longer than in nonfailing control hearts. The major underlying mechanisms for this prolongation are the enhanced activity of the Na+-Ca2+ exchanger, the slowed diastolic decay of the [Ca2+]i transient, and the reduction of the inwardly rectifying K+ current and the Na+-K+ pump current in myocytes of failing hearts. Furthermore, the fast and slow components of the delayed rectifier K+ current (I(Kr) and I(Ks), respectively) are of utmost importance in determining repolarization of the human ventricular action potential. In contrast, the influence of the transient outward K+ current on APD is only small in both cell groups. Inhibition of I(Kr) promotes the development of early afterdepolarizations in failing, but not nonfailing, myocytes. Furthermore, spontaneous Ca2+ release from the sarcoplasmic reticulum triggers a premature action potential only in failing myocytes. This model of the ventricular action potential and its alterations in heart failure is intended to serve as a tool for investigating the effects of therapeutic interventions on the electric excitability of the human ventricular myocardium.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Priebe, Beuckelmann. (1998) - version02
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
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.
2005-01-01 | MODEL8683876463 | BioModels
Project description:This a model from the article:
A mathematical model of the electrophysiological alterations in rat ventricular myocytes in type-I diabetes.
Pandit SV, Giles WR, Demir SS. Biophys J.
2003;84(2 Pt 1):832-41. 12547767
,
Abstract:
Our mathematical model of the rat ventricular myocyte (Pandit et al., 2001) was utilized to explore the ionic mechanism(s) that underlie the altered electrophysiological characteristics associated with the short-term model of streptozotocin-induced, type-I diabetes. The simulations show that the observed reductions in the Ca(2+)-independent transient outward K(+) current (I(t)) and the steady-state outward K(+) current (I(ss)), along with slowed inactivation of the L-type Ca(2+) current (I(CaL)), can result in the prolongation of the action potential duration, a well-known experimental finding. In addition, the model demonstrates that the slowed reactivation kinetics of I(t) in diabetic myocytes can account for the more pronounced rate-dependent action potential duration prolongation in diabetes, and that a decrease in the electrogenic Na(+)-K(+) pump current (I(NaK)) results in a small depolarization in the resting membrane potential (V(rest)). This depolarization reduces the availability of the Na(+) channels (I(Na)), thereby resulting in a slower upstroke (dV/dt(max)) of the diabetic action potential. Additional simulations suggest that a reduction in the magnitude of I(CaL), in combination with impaired sarcoplasmic reticulum uptake can lead to a decreased sarcoplasmic reticulum Ca(2+) load. These factors contribute to characteristic abnormal [Ca(2+)](i) homeostasis (reduced peak systolic value and rate of decay) in myocytes from diabetic animals. In combination, these simulation results provide novel information and integrative insights concerning plausible ionic mechanisms for the observed changes in cardiac repolarization and excitation-contraction coupling in rat ventricular myocytes in the setting of streptozotocin-induced, type-I diabetes.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Pandit, Giles, Demir. (2003) - version02
The original CellML model was created by:
Noble, Penny,
penny.noble@dpag.ox.ac.uk
University of Oxford
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
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.
2005-01-01 | MODEL8685104549 | BioModels
Project description:This a model from the article:
A novel computational model of the human ventricular action potential and Ca
transient.
Grandi E, Pasqualini FS, Bers DM. J Mol Cell Cardiol
2010 Jan;48(1):112-21 19835882
,
Abstract:
We have developed a detailed mathematical model for Ca handling and ionic
currents in the human ventricular myocyte. Our aims were to: (1) simulate basic
excitation-contraction coupling phenomena; (2) use realistic repolarizing K
current densities; (3) reach steady-state. The model relies on the framework of
the rabbit myocyte model previously developed by our group, with subsarcolemmal
and junctional compartments where ion channels sense higher [Ca] vs. bulk
cytosol. Ion channels and transporters have been modeled on the basis of the
most recent experimental data from human ventricular myocytes. Rapidly and
slowly inactivating components of I(to) have been formulated to differentiate
between endocardial and epicardial myocytes. Transmural gradients of Ca handling
proteins and Na pump were also simulated. The model has been validated against a
wide set of experimental data including action potential duration (APD)
adaptation and restitution, frequency-dependent increase in Ca transient peak
and [Na](i). Interestingly, Na accumulation at fast heart rate is a major
determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange
currents. We investigated the effects of blocking K currents on APD and
repolarization reserve: I(Ks) block does not affect the former and slightly
reduces the latter; I(K1) blockade modestly increases APD and more strongly
reduces repolarization reserve; I(Kr) blockers significantly prolong APD, an
effect exacerbated as pacing frequency is decreased, in good agreement with
experimental results in human myocytes. We conclude that this model provides a
useful framework to explore excitation-contraction coupling mechanisms and
repolarization abnormalities at the single myocyte level. Copyright 2009
Elsevier Inc. All rights reserved.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Grandi E, Pasqualini FS, Bers DM. (2009) - version=1.0
The original CellML model was created by:
Geoffrey Nunns
gnunns1@jhu.edu
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
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.
2005-01-01 | MODEL1006230092 | BioModels
Project description:Abnormalities of ventricular action potential (AP) cause malignant cardiac arrhythmias and sudden cardiac death. Here, we sought to identify microRNAs (miRNAs) that regulate the human cardiac AP and asked whether their manipulation allows for therapeutic modulation of AP abnormalities. Quantitative analysis of the miRNA targetomes in human cardiac myocytes identified miR-365 as a primary miRNA to regulate repolarizing ion channels. AP recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs) showed that elevation of miR-365 level significantly prolonged AP duration in hiPSC-CMs derived from a Short-QT syndrome (SQTS) patient, whereas specific inhibition of miR-365 normalized pathologically prolonged AP in Long-QT syndrome (LQTS) iPSC-CMs. Transcriptome analyses in human iPSC-CMs at bulk and single-cell level corroborated the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional AP-regulating genes by this miRNA. Whole-cell patch clamp experiments revealed miR-365-based regulation of repolarizing ionic currents. Finally, refractory period measurements in human myocardial slices substantiated the prolonging effect of miR-365 on AP duration also in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac AP duration by targeting key factors of cardiac repolarization.
2021-12-01 | GSE185687 | GEO
Project description:Abnormalities of ventricular action potential (AP) cause malignant cardiac arrhythmias and sudden cardiac death. Here, we sought to identify microRNAs (miRNAs) that regulate the human cardiac AP and asked whether their manipulation allows for therapeutic modulation of AP abnormalities. Quantitative analysis of the miRNA targetomes in human cardiac myocytes identified miR-365 as a primary miRNA to regulate repolarizing ion channels. AP recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs) showed that elevation of miR-365 level significantly prolonged AP duration in hiPSC-CMs derived from a Short-QT syndrome (SQTS) patient, whereas specific inhibition of miR-365 normalized pathologically prolonged AP in Long-QT syndrome (LQTS) iPSC-CMs. Transcriptome analyses in human iPSC-CMs at bulk and single-cell level corroborated the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional AP-regulating genes by this miRNA. Whole-cell patch clamp experiments revealed miR-365-based regulation of repolarizing ionic currents. Finally, refractory period measurements in human myocardial slices substantiated the prolonging effect of miR-365 on AP duration also in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac AP duration by targeting key factors of cardiac repolarization.
2021-12-01 | GSE185689 | GEO
Project description:Abnormalities of ventricular action potential (AP) cause malignant cardiac arrhythmias and sudden cardiac death. Here, we sought to identify microRNAs (miRNAs) that regulate the human cardiac AP and asked whether their manipulation allows for therapeutic modulation of AP abnormalities. Quantitative analysis of the miRNA targetomes in human cardiac myocytes identified miR-365 as a primary miRNA to regulate repolarizing ion channels. AP recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs) showed that elevation of miR-365 level significantly prolonged AP duration in hiPSC-CMs derived from a Short-QT syndrome (SQTS) patient, whereas specific inhibition of miR-365 normalized pathologically prolonged AP in Long-QT syndrome (LQTS) iPSC-CMs. Transcriptome analyses in human iPSC-CMs at bulk and single-cell level corroborated the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional AP-regulating genes by this miRNA. Whole-cell patch clamp experiments revealed miR-365-based regulation of repolarizing ionic currents. Finally, refractory period measurements in human myocardial slices substantiated the prolonging effect of miR-365 on AP duration also in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac AP duration by targeting key factors of cardiac repolarization.
2021-12-01 | GSE185688 | GEO
Project description:This a model from the article:
A mathematical model of a rabbit sinoatrial node cell.
Demir SS, Clark JW, Murphey CR, Giles WR. Am J Physiol
1994 Mar;266(3 Pt 1):C832-52 8166247
,
Abstract:
A mathematical model for the electrophysiological responses of a rabbit
sinoatrial node cell that is based on whole cell recordings from enzymatically
isolated single pacemaker cells at 37 degrees C has been developed. The ion
channels, Na(+)-K+ and Ca2+ pumps, and Na(+)-Ca2+ exchanger in the surface
membrane (sarcolemma) are described using equations for these known currents in
mammalian pacemaker cells. The extracellular environment is treated as a
diffusion-limited space, and the myoplasm contains Ca(2+)-binding proteins
(calmodulin and troponin). Original features of this model include 1) new
equations for the hyperpolarization-activated inward current, 2) assessment of
the role of the transient-type Ca2+ current during pacemaker depolarization, 3)
inclusion of an Na+ current based on recent experimental data, and 4)
demonstration of the possible influence of pump and exchanger currents and
background currents on the pacemaker rate. This model provides acceptable fits
to voltage-clamp and action potential data and can be used to seek biophysically
based explanations of the electrophysiological activity in the rabbit sinoatrial
node cell.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Demir SS, Clark JW, Murphey CR, Giles WR. (1994) - version01
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@aukland.ac.nz
The University of Auckland
The Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
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.
2005-01-01 | MODEL0912887467 | BioModels
Project description:This a model from the article:
A model for human ventricular tissue.
ten Tusscher KH, Noble D, Noble PJ, Panfilov AV. Am J Physiol Heart Circ Physiol
2004 Apr;286(4):H1573-89. 14656705
,
Abstract:
The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
ten Tusscher KH, Noble D, Noble PJ, Panfilov AV. (2004 - version05
The original CellML model was created by:
Noble, Penny, J
penny.noble@dpag.ox.ac.uk
Oxford University
Department of Physiology, Anatomy & Genetics
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/).
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
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.
2005-01-01 | MODEL0393108880 | BioModels