Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study (Original model in steady state)

Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study.

Model Status

This model has been curated and validated by Penny Noble of Oxford University and is known to run in PCEnv and COR to recreate the published results. The units have been checked and they are consistent. Note that this is the model in steady state and it is the original Faber Rudy model from 2000.

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 original paper reference is cited below:

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.