Minimal model for calcium alternans due to SR release refractoriness.

In the heart, rapid pacing rates may induce alternations in the strength of cardiac contraction, termed pulsus alternans. Often, this is due to an instability in the dynamics of the intracellular calcium concentration, whose transients become larger and smaller at consecutive beats. This alternation has been linked experimentally and theoretically to two different mechanisms: an instability due to (1) a strong dependence of calcium release on sarcoplasmic reticulum (SR) load, together with a slow calcium reuptake into the SR or (2) to SR release refractoriness, due to a slow recovery of the ryanodine receptors (RyR2) from inactivation.

Are SR Ca content fluctuations or SR refractoriness the key to atrial cardiac alternans?: insights from a human atrial model.

Despite the important role of electromechanical alternans in cardiac arrhythmogenesis, its molecular origin is not well understood. The appearance of calcium alternans has often been associated to fluctuations in the sarcoplasmic reticulum (SR) Ca loading. However, cytosolic calcium alternans observed without concurrent oscillations in the SR Ca content suggests an alternative mechanism related to a dysfunction in the dynamics of the ryanodine receptor (RyR2).

Dependency of calcium alternans on ryanodine receptor refractoriness.

Background: Rapid pacing rates induce alternations in the cytosolic calcium concentration caused by fluctuations in calcium released from the sarcoplasmic reticulum (SR). However, the relationship between calcium alternans and refractoriness of the SR calcium release channel (RyR2) remains elusive.

Methodology/principal Findings: To investigate how ryanodine receptor (RyR2) refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model.

Cardiac dynamics: a simplified model for action potential propagation.

This paper analyzes a new semiphysiological ionic model, used recently to study reexitations and reentry in cardiac tissue [I.R. Cantalapiedra et al, PRE 82 011907 (2010)].

Phase-2 reentry in cardiac tissue: role of the slow calcium pulse.

Phase-2 re-entry is thought to underlie many causes of idiopathic ventricular arrhythmias as, for instance, those occurring in Brugada syndrome. In this paper, we study under which circumstances a region of depolarized tissue can re-excite adjacent regions that exhibit shorter action potential duration (APD), eventually inducing reentry. For this purpose, we use a simplified ionic model that reproduces well the ventricular action potential.

Reexcitation mechanisms in epicardial tissue: role of I(to) density heterogeneities and I(Na) inactivation kinetics.

Dispersion of action potential repolarization is known to be an important arrhythmogenic factor in cardiopathies such as Brugada syndrome. In this work, we analyze the effect of a variation in sodium current (I(Na)) inactivation and a heterogeneous rise of transient outward current (I(to)) in the probability of reentry in epicardial tissue. We use the Luo-Rudy model of epicardial ventricular action potential to study wave propagation in a one-dimensional fiber.