We simulate currents and concentration profiles generated by Ca(2+) release from the endoplasmic reticulum (ER) to the cytosol through IP(3) receptor channel clusters. Clusters are described as conducting pores in the lumenal membrane with a diameter from 6 nm to 36 nm. The endoplasmic reticulum is modeled as a disc with a radius of 1-12 microm and an inner height of 28 nm. We adapt the dependence of the currents on the trans Ca(2+) concentration (intralumenal) measured in lipid bilayer experiments to the cellular geometry. Simulated currents are compared with signal mass measurements in Xenopus oocytes. We find that release currents depend linearly on the concentration of free Ca(2+) in the lumen. The release current is approximately proportional to the square root of the number of open channels in a cluster. Cytosolic concentrations at the location of the cluster range from 25 microM to 170 microM. Concentration increase due to puffs in a distance of a few micrometers from the puff site is found to be in the nanomolar range. Release currents decay biexponentially with timescales of <1 s and a few seconds. Concentration profiles decay with timescales of 0.125-0.250 s upon termination of release.

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field.

In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca 2+ movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca 2+ release sites and physiological Ca 2+ flux parameters, coupled with a computationally inexpensive framework. By translating nonlinear Ca 2+ excitability into threshold dynamics, we avoid the computationally demanding time stepping of the partial differential equations that are often used to model Ca 2+ transport. Our approach successfully reproduces key features of atrial myocyte Ca 2+ signaling observed using confocal imaging. In particular, the model displays the centripetal Ca 2+ waves that occur within atrial myocytes during excitation-contraction coupling, and the effect of positive inotropic stimulation on the spatial profile of the Ca 2+ signals. Beyond this validation of the model, our simulation reveals unexpected observations about the spread of Ca 2+ within an atrial myocyte. In particular, the model describes the movement of Ca 2+ between ryanodine receptor clusters within a specific z disk of an atrial myocyte. Furthermore, we demonstrate that altering the strength of Ca 2+ release, ryanodine receptor refractoriness, the magnitude of initiating stimulus, or the introduction of stochastic Ca 2+ channel activity can cause the nucleation of proarrhythmic traveling Ca 2+ waves. The model provides clinically relevant insights into the initiation and propagation of subcellular Ca 2+ signals that are currently beyond the scope of imaging technology.A human heart beats more than a billion times during the average lifespan, and is required to do so with great fidelity. The ventricular chambers of the heart are responsible for generating the force that propels blood to the lungs and body (1). Under sedentary conditions, the atrial chambers make only a minor contribution to blood pumping. However, during periods of increased hemodynamic demand, such as exercise, atrial contraction increases to enhance the amount of blood within the ventricles before they contract. This "atrial kick" is believed to account for up to 30% extra blood-pumping capacity. Deterioration of atrial myocytes with aging causes the loss of this blood-pumping reserve, thereby increasing frailty in the elderly. Atrial kick is also lost during atrial fibrillation (AF), the most common form of cardiac arrhythmia. The stagnation of blood within the atrial chambers during AF can cause thrombus formation, leading to thromboembolism. Approximately 15% of all strokes occur in people with AF. As shown in numerous reports, the genesis and maintenance of AF is causally linked to the dysregulation of Ca 2+ signaling (2-4). Detailed characterization of Ca 2+ movement within atrial myocytes is therefore necessary to understand changes involved in aging and conditions such as AF.Elevation of the cytosolic Ca 2+ concentration is the trigger for contraction of cardiac myocytes (1). Engageme...

We define Landau quasiparticles within the Gutzwiller variational theory and derive their dispersion relation for general multiband Hubbard models in the limit of large spatial dimensions D. Thereby we reproduce our previous calculations which were based on a phenomenological effective single-particle Hamiltonian. For the one-band Hubbard model we calculate the first-order corrections in 1/D and find that the corrections to the quasiparticle dispersions are small in three dimensions. They may be largely absorbed in a rescaling of the total bandwidth, unless the system is close to half band filling. Therefore, the Gutzwiller theory in the limit of large dimensions provides quasiparticle bands which are suitable for a comparison with real, three-dimensional Fermi liquids.

Whereas Ca(2+) signalling in ventricular cardiomyocytes is well described, much less is known regarding the Ca(2+) signals within atrial cells. This is surprising given that atrial cardiomyocytes make an important contribution to the refilling of ventricles with blood, which enhances the subsequent ejection of blood from the heart. The dependence of cardiac function on the contribution of atria becomes increasingly important with age and exercise. Disruption of the rhythmic beating of atrial cardiomyocytes can lead to life-threatening conditions such as atrial fibrillation. Atrial and ventricular myocytes have many structural and functional similarities. However, one key structural difference, the lack of transverse tubules ("T-tubules") in atrial myocytes, make these two cell types display vastly different calcium patterns in response to electrical excitation. The lack of T-tubules in atrial myocytes means that depolarisation provokes calcium signals that originate around the periphery of the cells. Under resting conditions, such Ca(2+) signals do not propagate towards the centre of the atrial cells and so do not fully engage the contractile machinery. Consequently, contraction of atrial myocytes under resting conditions is modest. However, when atrial myocytes are stimulated with a positive inotropic agonist, such as isoproterenol, the peripheral Ca(2+) signals trigger a global wave of Ca(2+) that propagates in a centripetal manner into the cells. Enhanced centripetal movement of Ca(2+) in atrial myocytes leads to increased contraction and a more substantial contribution to blood pumping. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.