Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study
Catherine
Lloyd
Auckland Bioengineering Institute
Model Status
This model has been curated and is known to run in PCEnv and COR to recreate the published results. The units have been checked and are known to be consistent. The CellML model has been based on a translation of the LRd07 Matlab code which can be downloaded from the Rudy lab website. It is basically the Faber and Rudy 2000 model with the addition of a transient potassium current (Ito) and an updated Irel current.
Model Structure
ABSTRACT: Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration (APD) shortens in two phases, a rapid phase without Na(+) accumulation and a slower phase that depends on [Na(+)](i). 2) The rapid APD shortening is due to incomplete deactivation (accumulation) of I(Ks). 3) The slow phase is due to increased repolarizing currents I(NaK) and reverse-mode I(NaCa), secondary to elevated [Na(+)](i). 4) Na(+)-overload slows the rate of AP depolarization, allowing time for greater I(Ca(L)) activation; it also enhances reverse-mode I(NaCa). The resulting increased Ca(2+) influx triggers a greater [Ca(2+)](i) transient. 5) Reverse-mode I(NaCa) alone can trigger Ca(2+) release in a voltage and [Na(+)](i)-dependent manner. 6) During I(NaK) block, Na(+) and Ca(2+) accumulate and APD shortens due to enhanced reverse-mode I(NaCa); contribution of I(K(Na)) to APD shortening is negligible. By slowing AP depolarization (hence velocity) and shortening APD, Na(+)-overload acts to enhance inducibility of reentrant arrhythmias. Shortened APD with elevated [Ca(2+)](i) (secondary to Na(+)-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.
The complete original paper reference is cited below (but again please note that this CellML model is not the exact Faber-Rudy model, instead it is based on a translation of the LRd07 Matlab code which can be downloaded from the Rudy lab website. It is similar to the Faber and Rudy 2000 model with the addition of a transient potassium current (Ito) and an updated Irel current.):
Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study, Gregory M. Faber and Yoram Rudy, 2000, Biophysical Journal, 78, 2392-2404. PubMed ID: 10777735
cell diagram of the shaw and viswanathan models showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum
A schematic diagram of the Faber and Rudy 2000 cardiac myocyte model.
The University of Auckland
Auckland Bioengineering Institute
Catherine Lloyd
Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study (Modified Model)
Auckland Bioengineering Institute, The University of Auckland
This model has been curated and is known to run in PCEnv and COR to recreate the published results. The units have been checked and are known to be consistent.
The CellML model has been based on a translation of the LRd07 Matlab code which can be downloaded from the Rudy lab website. It is basically the Faber and Rudy 2000 model with the addition of a transient potassium current (Ito) and an updated Irel current.
j.ashton@auckland.ac.nz
keyword
excitation-contraction coupling
Ventricular Myocyte
calcium
electrophysiology
cardiac
pathology
ventricular myocyte
Y
Rudy
Jesse
Ashton
Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study
78
2392
2404
2000-05-00 00:00
Biophysical Journal
2008-08-01T00:00:00+00:00
10777735
G
Faber
M