Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study (Updated model with an added Ito current and and updated Irel current)

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

A schematic diagram of the Faber and Rudy 2000 cardiac myocyte model.